1. Richard Rapoza February 25, 2013
Update on the Development of BVS: Challenges for the Development of Polymeric Biodegradable Scaffolds for Peripheral Vascular Intervention
Richard Rapoza
February 25, 2013

2. Full-time employee of Abbott Vascular
Richard J. Rapoza, PhD
Full-time employee of Abbott Vascular

3. Clinical Goals of Minimally Invasive SFA Treatment
Acute Outcomes
Re-establish flow with a uniform vessel appearance
Minimize acute vessel closure and recoil or geometrical disturbance
Long Term Outcomes
Sustain Patency (hyperplasia, constrictive remodeling)
Minimize long term thrombosis risk
Permit future re-treatment

4. Multiple Approaches Angioplasty Atherectomy Balloon Expandable Stents
POBA
Drug Coated Balloons
Atherectomy
Balloon Expandable Stents
Self-Expanding Stents (SES)
Bare Metal Stents
Drug Eluting Stents
Covered Stents
Bioresorbable Vascular Scaffolding (BVS)
Bare BVS
Drug Eluting BVS*
* Drug Eluting BVS for the peripheral arteries in an investigational device outside the U.S. Not available for sale.

5. The SFA Applies Dynamic Forces
SFA Challenges
Shortening
18 mm
Increased Curvature
0.04 cm
Twist
46 degrees
Flexion Points (>15 degrees)
2/10
Klein et al. Catheter Cardiovasc Interv 2009;74:799.

6. Lesion Length Impacts Primary Patency Regardless of Treatment Modality
Worse results in long SFA lesions …
Good results in short lesions
with SES, DCB, and DES…
Adapted from Shroë H. Superficial Femoral Artery PTA or Stenting 5 year results. CIRSE 2011.

7. High Chronic Outward Force Leads to Chronic Stent-Vessel Irritation
Sizing Example
Optimal Oversizing
Medium Oversizing
High Oversizing
8 mm stent compressed to:
7.3 – 6.2 mm
6.2 – 5.0 mm
5.0 – 4.2 mm
Stent
Stent
Stent
Note: Preclinical animal models.
Zhao HQ et. al. Cardiovasc Intervent Radiol 2009;32:

8. Preliminary DES Studies Primary Patency
Drug Eluting Stents vs. Bare Metal Stents
VIENNA vs. STRIDES vs. SIROCCO
Adapted from Lammer J. First In-man Clinical Trial of an self expandable Everolimus-coated Stent in the SFA. ISET 2010.

9. Recent DES Data Freedom from TLR After 5 Years
Ave. Lesion Length = 15494 mm
Stent Type n
Everflex™ 323
Zilver® PTX® 216
Astron® 111
Astron® Pulsar® 95
Lifestent® 51
S.M.A.R.T.® 13
Luminexx® 12
Complete® SE 6
Total 827
Bosiers M. 5-year evaluation of SFA stenting (Belgian/German study). VEITH 2012.

10. Post Drug Elution, Chronic Irritation Remains
6 mm stents deployed at 6 mm and compressed to 3 mm
Model with Leg Motion and Blood Pressure
Test(s) performed by and data on file at Abbott Vascular.

11. Clinical Impact of SFA Treatment Modalities
Best
Preferred Solution
Drug Eluting BVS
Metallic
Stents
Acute
Outcome
Atherectomy
DCB
PTA
Worst
Best
Long-Term Outcome
BVS for the peripheral arteries in an investigational device outside the U.S. Not available for sale.

12. Bioresorbable Scaffold Bioresorbable Coating
Drug Eluting BVS
Bioresorbable Scaffold
Bioresorbable Coating
Everolimus
Delivery System
Poly(L-lactide) (PLLA)
Naturally resorbed, fully metabolized
Designed for SFA and iliac arteries
Poly(D,L-lactide) (PDLLA) coating
Naturally resorbed, fully metabolized
100 μg/cm2
Balloon- expandable delivery system
035” OTW platform .
BVS for the peripheral arteries in an investigational device outside the U.S. Not available for sale.
All illustrations are artists’ renditions. Illustrations created by Abbott. 12 12

13. Drug Eluting BVS Phases of Functionality
Revascularization
Restoration
Stabilize
Disappear
Mass
Support
Drug Elution
Lumen stabilization and scaffold disappearance are the key ingredients for a durable SFA therapy.
Combining endovascular legacy with deep coronary BVS experience creates a specialized platform to address long term SFA needs
ANIMATED SLIDE: TWO CLICKS: (1) Stabilize, (2) Disappear and text at bottom.
BVS for the peripheral arteries in an investigational device outside the U.S. Not available for sale.

14. Vascular Response to BVS at 2, 3, 4 Years Arterial Integration and Accommodation
Mass loss data suggests 100% of material mass has been lost within years
The shape of struts is still apparent at 2 years, although the device is fully resorbed
No inflammation around the pre-existing strut regions
BVS
Alcian Blue Stain:
Proteoglycan
1 year
2 years
3 years
4 years
3 years: struts fully replaced by tissue
10x
4 years: sites of pre-existing struts are indiscernible
Representative photomicrographs of porcine coronary arteries, 2x
Cypher
BVS for the peripheral arteries in an investigational device outside the U.S. Not available for sale. Photos taken by and on file at Abbott Vascular. Tests performed by and data on file at Abbott Vascular. Representative preclinical data from porcine coronary arteries, 2x objective. 14

15. Chronic Deformation Effects on Neointima
Leg flexion causes stent deformation and neointimal formation
Drug Eluting BVS
Oversized Nitinol SES
Test(s) performed by and data on file at Abbott Vascular. Healthy porcine iliofemoral artery at 12 months.

16. BVS Technically Designed for Physiological Needs and Clinical Goals
Clinical goals drive the scaffold design, as governed by the relationship between scaffold function and physiological need
Clinical Goal
Physiological Need
Scaffold Function
Re-establish laminar flow with a uniform angiographic appearance
Minimize acute vessel closure and recoil or geometrical disturbance
Acutely provide radial support to the vessel
Restore natural vessel function
Support vessel until stabilized, then allow unconstrained vessel movement
Form a vessel:scaffold composite and develop predictable discontinuities
Establish durable result while permitting potential for future re-treatment
Prevent long term vessel damage from persistent irritation and/or chronic outward force
Naturally resorb, fully metabolize
Serruys PW, Onuma Y, Ormiston JA, et al. Circulation. 2010;122(22):
Ormiston JA, Serruys PW, Onuma Y, et al. Circ. Cardiovasc. Interv. 2012;5(5):
BVS for the peripheral arteries in an investigational device outside the U.S. Not available for sale.

17. Crush Recovery Comparison Balloon Expandable Stent vs
Crush Recovery Comparison Balloon Expandable Stent vs. Balloon Expandable BVS
BVS for the peripheral arteries in an investigational device outside the U.S. Not available for sale. This video demonstrates the physical
properties and capabilities of PLLA-based bioresorbable scaffolds. Tests performed by and data on file at Abbott Vascular.

18. Designed Loss of Continuity
Basic design concept: rings joined by links
Link
Ring
Design decouples radial support and axial flexibility
Rings provide resistance to radial loads
Links provide flexibility to navigate tortuous paths and conformability to match vessel curvature
It is acceptable for links become discontinuous prior to rings, because they are not necessary for support
BVS for the peripheral arteries in an investigational device outside the U.S. Not available for sale. Photos taken by and on file at Abbott Vascular.
Tests performed by and data on file at Abbott Vascular. All illustrations are artists’ renditions. Illustrations created by Abbott.

19. ESPRIT I Trial Design
A single de novo lesion in the superficial femoral (SFA) or iliac arteries in patients with symptomatic claudication (Rutherford Becker Category 1-3)
Prospective, Single Arm, Multi-Center OUS trial evaluating the Esprit BVS (N=35)
One target lesion treated with a single 6.0 x 58 mm Esprit BVS
Vessel diameter from ≥ 5.5 – ≤ 6.5 mm, segment length ≤ 50 mm
Baseline 1 mo 6 mo 12 mo 2 yr 3 yr
Clinical, Duplex (all subjects)
Angiography (all subjects)
IVUS Substudy (N ~ 10)
MSCT/ MR Substudies (N ~ 5 each)
PK Sub Study (N ~ 10, out to 1 mo.)
Trial Objective:
Endpoints:
Evaluate safety and performance of the Esprit BVS in subjects with symptomatic atherosclerotic disease of the SFA or iliac arteries
Procedural, clinical, functional, hemodynamic, angiographic, IVUS, non-invasive imaging in-hospital and at F/U time points indicated
BVS for the peripheral arteries in an investigational device outside the U.S. Not available for sale.

20. ESPRIT I Lesion Characteristics
ESPRIT (N=35)
External Iliac (%)
SFA (%)
11.4
84.0:
Proximal
14.3
Mid
31.4
Distal
54.3
Target lesion length (mm)
35.49 ± 15.74
Total occlusions (%)
28.0
Occlusion length (mm)
30.6 ± 15.7
Scheinert D. ESPRIT I Clinical Study 30-day results: LINC Course BVS for the peripheral arteries in an investigational device outside the U.S. Not available for sale. 20

21. ESPRIT I Angiographic Results (Core Lab)
Pre-Procedure
(N=35)
Post-Procedure
Lesion length (mm)
35.49
---
In-segment RVD (mm)
4.85
4.91
In-segment MLD (mm)
1.01
4.25
Diameter Stenosis (%)
Median, (min, max)
80.04 ± 15.14
80.99, (42.1, 100.0)
13.07 ± 7.52
10.98, (2.63, 29.86)
Scheinert D. ESPRIT I Clinical Study 30-day results: LINC Course BVS for the peripheral arteries in an investigational device outside the U.S. Not available for sale. 21

22. ESPRIT I Key Study Endpoints
ESPRIT (N=34)
1-Month
Deaths
0.0%
Any amputation of treated limb
Bypass surgery of treated limb
Scaffold thrombosis
Target lesion revascularization (TLR)
Target vessel revascularization (TVR)
Target extremity revascularization (TER)
Binary restenosis
One subject withdrew consent for further follow-up.
Scheinert D. ESPRIT I Clinical Study 30-day results: LINC Course 2013.
BVS for the peripheral arteries in an investigational device outside the U.S. Not available for sale. 22

23. ESPRIT I Rutherford Becker Class and Ankle Brachial Index
ESPRIT baseline
(N=35)
ESPRIT 1-month
(N=34*)
Rutherford 0 (no claudication)
0 %
84.8 %
Rutherford 1 (mild claudication)
8.6 %
12.1 %
Rutherford 2 (moderate claudication)
34.3 %
3.0 %
Rutherford 3 (severe claudication)
57.1 %
ABI Median, (min, max)
0.75 ± 0.14
0.74, (0.45, 1.00)
1.00 ± 0.11
1.0 (0.45, 1.00)
Ankle Brachial Index (ABI)
A measure of the fall in blood pressure in the arteries supplying the legs is used to detect evidence of blockages in the peripheral vessels. It is calculated by dividing the higher systolic blood pressure in the ankle (dorsalis pedis or posterior tibial) of the one leg by the higher of the two systolic blood pressures in the arms. A doppler probe is used to monitor the pulse while a sphygmomanometer is inflated above the artery. The cuff is deflated and the pressure at which the pulse returns is recorded.
(Highest Ankle Systolic Pressure/Highest Brachial Systolic Pressure=ABI).
The ABI is the ratio of the ankle to arm pressure, and an ABI between 0.9 and 1.3 is considered normal. A reduced ABI (less than 0.9) is consistent with peripheral artery occlusive disease, with values below 0.8 indicating moderate disease and below 0.5 severe disease.
A value greater than 1.3 is considered abnormal suggesting calcification of the walls of the arteries and noncompressible vessels, reflecting severe peripheral vascular disease. For subjects in whom the ABI cannot be accurately measured (medial arterial calcification), toe pressure measurement and determination of the toe brachial index should be used.
Scheinert D. ESPRIT I Clinical Study 30-day results: LINC Course BVS for the peripheral arteries in an investigational device outside the U.S. Not available for sale. 23

24. Conclusions
Self expanding metallic stents can impart chronic injury through oversizing / chronic outward force and local strut/cell movement
Drug elution is effective only while present in tissue. Once elution ceases, and drug is metabolized, chronic injury will continue unmasked.
Fully resorbable scaffolds have the potential to pave effectively after intervention to:
Sustain lumen dimensions while vessel wall heals
Disappear mechanically and not cause chronic injury
Fully resorb to restore mechanical integrity to the vessel wall
BVS for the peripheral arteries in an investigational device outside the U.S. Not available for sale.

25. Abbott Vascular
3200 Lakeside Dr., Santa Clara, CA USA, Tel:
Tests performed by and data on file at Abbott Vascular. All illustrations included are artist’s renditions. Not drawn to scale. All photos taken by and on file at Abbott Vascular.
BVS for the peripheral anatomies is an investigational device outside the United States. ESPRIT I is an Abbott sponsored clinical trial outside the United States. Astron and Astron Pulsar are trademarks of Biotronik SE & Co. KG. Lifestent and Luminexx are trademarks of C. R. Bard. Zilver and Zilver PTX are trademarks of Cook Medical. Everflex is a trademark of Covidien. S.M.A.R.T. is a trademark of the Cordis Corporation, a Johnson & Johnson company. Complete SE is a trademark of Medtronic, Inc.
©2013 Abbott. All rights reserved. AP US Rev. A 02/13