1. Novel Stent Technologies: Update on Bioresorbable Stents
Chuck Simonton, MD, FACC, FSCAI Chief Medical Officer
Abbott Vascular
Santa Clara, CA, USA
CRT 2013

2. Chief Medical Officer Abbott Vascular, Santa Clara, CA
Charles A. Simonton, MD
Chief Medical Officer
Abbott Vascular, Santa Clara, CA

3. Programs Update: Fully Bioresorbable Scaffolds
Commercial authorization outside the United States*
Abbott Vascular
Companies with human experience
Biotronik
Reva Medical
Elixir Medical
Arterial Remodeling Technologies (ART)
Kyoto Medical Planning (no recent activity in coronaries)
Additional effort w/o human experience
OrbusNeich
Amaranth Medical
Xenogenics/MultiCell (technology acquired from BTI)
Biosensors
No recent efforts
Boston Scientific
Cordis/J&J
Medtronic
*CAUTION: Investigational device limited by Federal (US) law to investigational use only.

4. Biotronik
Serruys, P.W., PCR 2012

5. Reva Medical ReZolveTM
Second generation device – ReZolveTM
Scaffold design:
Slotted/spiral design
7F guide catheter compatible (protective sheath)
Strut thickness ~100; profile 1.83 mm
3.0 mm device can be expanded to 3.7 mm
Treat vessels 2.9 to 3.4 mm
Scaffold material:
Tyrosine-based polycarbonate copolymer (Surmodics)
Second generation device incorporates covalently bonded iodine to enhance radiopacity
Drug:
Sirolimus – 80 µg
Thin coating -  5 µm, abluminal
Kaluza, G. CRT 2011
Abizaid, A, TCT 2012

6. Reva RESTORE Clinical Strategy
Costa, R., TCT 2012

7. Elixir DESolveTM Scaffold Design Scaffold Material Drug
Markers at either end (see photo)
3.0, 3.25, and 3.5 mm diameters; 14 and 18 mm lengths
2.5 mm, 2.75 mm and 3.75 mm available later
Strut thickness = 150 µm; profile 0.058”
Scaffold is protected by peel-away sheath
Scaffold Material
PLLA-based
Fully resorbed in 1-2 years
Drug
FIM device: Myolimus, licensed from Novartis (3 µg/mm)
CE device: Novolimus (5 µg/mm); internally developed mTOR inhibitor
Marker Beads
Peel-Away Sheath
Verheye, S. TCT 2012
Abizaid, A. CRT 2012
Verheye, S. TCT 2011 (live case)

8. Elixir DESolve FIM Trial
Angiographic Results at 6 Months
Verheye, S., PCR 2012

9. Arterial Remodeling Technologies (ART)
Fajadet, J. TCT 2012

10. Arterial Remodeling Technologies (ART)
Fajadet, J. TCT 2012

11. The Abbott Vascular Bioresorbable Vascular Scaffold: AbsorbTM11

12. Total Absorb Pts Studied
Comprehensive Clinical Trial Program Absorb™
2011
2012
2013
2014
2015
2016
ABSORB Cohort A n = 30; FIM
5 Y
ABSORB Cohort B n = 101; FIM
1 Y
2 Y
3 Y
4 Y
5 Y
ABSORB Extend n = up to 1,000
Enrollment & Follow-Up
1 Y
2 Y
3 Y
ABSORB II n = ~330
Enrollment & Follow-Up
1 Y
2 Y
3 Y
ABSORB PHYSIOLOGY n = ~35
Enrollment & Follow-Up
1 Y
2 Y
ABSORB FIRST* n = 10,000
Enrollment & Follow-Up
1 Y
2 Y
ABSORB III n = ~1,502
Enrollment & Follow-Up
1 Y
2 Y
3 Y
Please note patients studied are Absorb patients only.
ABSORB Japan n = ~265
Enrollment & Follow-Up
1 Y
2 Y
ABSORB China n = ~200
Enrollment & Follow-Up
2 Y
1 Y
Total Absorb Pts Studied
n=~599
n~965
n~5,709
n~13,463
n~13,463
n~13,463
>2,300 patients treated to date reflects clinical trial patients plus non-trial, real-world experience.
Note: Sample sizes reflect ABSORB patients only.
* n= 10,000 f/u at 6 months patients f/u at 1 -3 years, patients at 2-4 years
Smits, P. – ABSORB Cohort B1 – 3 year data, TCT 2012
Absorb Cohort B, Extend, II, Physiology, First, Japan and China are ongoing clinical trials outside the United States.

13. 30 subjects (Non-randomized) 4 sites in Europe & New Zealand
ABSORB Cohort A
30 subjects (Non-randomized) 4 sites in Europe & New Zealand
Clinical
Follow-Up (Months) 6 12 18 24 36 48 60
QCA, IVUS, OCT, IVUS VH
MSCT
Study Objective
First In Man, Single Arm – safety/performance
Endpoints
Typical PCI clinical and imaging endpoints
Treatment
Single, de novo native coronary lesion in a vessel with a reference vessel diameter of 3.0 mm
Device Sizes
3.0 x 12 mm scaffolds (3.0 x 18 mm scaffolds available after enrolment start and used in 2 pts)
This is the trial design for ABSORB Cohort A.
It included 30 patients. 6 sites participated in the trial, although only 4 sites actually enrolled patients.
Most patients were treated with a 3.0 x 12 mm device. A 3.0 x 18 mm device became available toward the end of enrollment and consequently only 2 patients were treated with that size device.
Ellis, S. - From ABSORB Cohort A to ABSORB III and IV Randomized Trials. April 2012.

14. ABSORB Cohort A Long-Term Data Out to 5 Years
ABSORB Cohort A Clinical Results at Each Phase: Intent to Treat
RESTORATION
RESORPTION
Hierarchical
6 Months 30 Patients
1 year 29 Patients**
2 Year 29 Patients**
5 Year
29 Patients**
Ischemia Driven MACE***
1 (3.3%)*
1 (3.4%)*
Cardiac Death
0 (0.0%) MI
Q-Wave MI
Non Q-Wave MI
Ischemia Driven TLR
by PCI
0 (0.%)
by CABG
No scaffold thrombosis by ARC or Protocol
* Same patient – this patient also underwent a TLR, not qualified as ID-TLR (DS = 42%)
** One patient withdrew consent and missed the 9, 12, 18 month and 2, 3, and 4 year visits; two patients died from a non-cardiac causes, one at 706 days and one at 888 days post procedure
*** MACE – Composite endpoint comprised of cardiac death, myocardial infarction (MI) and ischemia-driven target lesion revascularization (TLR) by PCI or CABG
Serruys, PW., TCT, 2011

15. ABSORB Cohort A – Intravascular Imaging at 5 years Scaffold Completely Resorbed and Vessel Healing Evident
Late lumen gain and characteristic ‘final golden tube’ on OCT
IVUS
OCT
ABSORB
Cohort A
MLA
6.35 mm2
6 month follow up
In fact, 5-year follow up of Cohort A patients is showing that late lumen gains at 2 years are preserved at 5 years. And the characteristic appearance of a so-called golden tube on OCT is indicative of the beneficial remodeling that can take place after scaffold resorption.
MLA
8.77 mm2
5 year follow up
The ‘final golden tube’
R.J. van Geuns, PCR Images courtesy of Thoraxcenter, Erasmus MC, Rotterdam, The Netherlands

16. ABSORB Cohort B
101 subjects (Non-randomized) 12 sites in Europe, Australia, New Zealand
Group B1 (n = 45)
Clinical Follow-Up (Months)
30 days 6 12 18 24 36 48 60
Group B2 (n = 56) QCA, IVUS, OCT, IVUS VH
MSCT
Study Objective
First In Man, Single Arm – safety/performance
Endpoints
Typical PCI clinical and imaging endpoints
Treatment
Up to 2 de novo lesions in different epicardial vessels Reference vessel diameter of 3.0 mm, lesions ≤ 14 mm in length
Device Sizes
3.0 x 18 mm devices
Trial design for Cohort B.
Enrolled 101 patients at 12 sites. Patients were divided into two groups: the first 45 patients come back for imaging follow-up at 6 and 24 months; the second group of 56 patients come back for imaging at 1 and 3 years.
Smits, P. – ABSORB Cohort B1 – 3 year data, TCT 2012

17. ABSORB Cohort B Group 1&2 Clinical Results - Intent to treat
30 Days
30 Days
6 Months
6 Months
1 Year
1 Year
2 Years
2 Years
Non -
Hierarchical
n = 101
n = 101
n = 101
n = 100*
Cardiac Death %
Cardiac Death %
Myocardial Infarction % (n)
Myocardial Infarction % (n)
2.0 (2)
2.0 (2)
3.0 (3)
3.0 (3)
3.0 (3)
3.0 (3)
3.0 (3)
3.0 (3) Q Q - -
wave MI
wave MI
Non Q
Non Q - -
wave MI
wave MI
2.0 (2)
2.0 (2)
3.0 (3)
3.0 (3)
3.0 (3)
3.0 (3)
3.0 (3)
3.0 (3)
Ischemia driven TLR % (n)
Ischemia driven TLR % (n)
2.0 (2)
2.0 (2)
4.0 (4)
4.0 (4)
6.0 (6)
6.0 (6)
CABG
CABG
PCI
PCI
2.0 (2)
2.0 (2)
4.0 (4)
4.0 (4)
6.0 (6)
6.0 (6)
Hierarchical MACE % (n)
Hierarchical MACE % (n)
2.0 (2)
2.0 (2)
5.0 (5)
5.0 (5)
6.9 (7)
6.9 (7)
9.0 (9)
9.0 (9)
MACE: Cardiac death, MI, ischemia-driven TLR - TVF: Cardiac death, MI, ischemia-driven TLR, ischemia-driven TVR
No scaffold thrombosis by ARC or Protocol out to 2 – Year only 2 additional TLR events between 1 year and 2 year
D. Dudek, ABSORB Cohort B Trial, Evaluation of the Absorb Everolimus Eluting Bioresorbable Vascular Scaffold (Absorb BVS) in the Treatment of Patients with de novo Native Coronary Artery Lesions, 2-Year Clinical Results, ACC / *One patient missed the 2 year FUP

18. Insight on evolution of late luminal loss over times
BVS 1.1 and Xience V (non-matched population)
6M BVS(Cohort B): 0.19±0.18 mm (N=42)
6M EES (SPIRIT I): 0.10±0.23 mm (N=22) mm

19. Insight on evolution of late luminal loss over times
BVS 1.1 and Xience V (non-matched population)
6M BVS(Cohort B): 0.19±0.18 mm (N=42)
6M EES (SPIRIT I): 0.10±0.23 mm (N=22) mm

20. 12 months Insight on evolution of late luminal loss over times
BVS 1.1 and Xience V (non-matched population)
12 months
12M BVS (Cohort B): 0.27 ± 0.25 mm (N=56)
12M EES (SPIRIT I): 0.23 ± 0.29 mm (N=22) mm

21. 24 months Insight on evolution of late luminal loss over times
BVS 1.1 and Xience V (non-matched population)
24 months
24M BVS (Cohort B): 0.27 ± 0.20 mm (N=38)
24M EES (SPIRIT II): 0.33 ± 0.37mm (N=96) mm

22. Time After Index Procedure (days)
Absorb™ BVS Low incidence of adverse events through 3 years
KM estimate of MACE rate in patients treated with Absorb BVS (ABSORB Cohort B, n=101)
ABSORB Cohort B1 – 3 year data
Time After Index Procedure (days) 37
194
284
393
573
758
1123
Absorb™ BVS(B1+B2) At Risk
101 99 96 94 92 91 41
Smits P. – ABSORB Cohort B1 – 3 year data, TCT 2012

23. Absorb™ Vasomotor Function Testing1
6 Months1
12 Months2
24 Months3
ABSORB Cohort B1
ABSORB Cohort B2
ABSORB Cohort A
(n=15)
(n=6)
(n=19)
(n=13)
(n=9)
(n=7)
0.5
Vasodilation
 in Vessel Diameter (mm)
(pre-drug infusion to post-drug infusion)
Vasoconstriction
-0.5
Acetylcholine
Methergine -1
1. Adapted from Serruys, PW. ACC / 2. Adapted from Serruys, PW. ACC / 3. Adapted from Serruys, PW, et al. Lancet 2009; 373:

24. Quantitative OCT Assessment of ABSORB BVS 1.1
Baseline
Follow-up
Strut area
Strut Core area
Strut Core area
Capitals in title
Lumen Area
Scaffold Area
Strut Core area
Neointimal area =Scaffold area – Lumen area –
Strut core area
van Geuns, R. – ABSORB Cohort B1 – 2 Yr OCT data, AHA 2011

25. Minimal scaffold area, mm²
Results of Quantitative OCT Serial Analysis
OCT
Post procedure
(n=23)
6 month
24 month
BL-2Y
Mean scaffold area, mm2
7.47±1.18
7.70 ± 1.34
8.24 ± 1.83
Minimal scaffold area, mm²
6.22 ± 1.26
6.17 ± 1.46
6.36 ± 1.41
Mean Strut core area, mm2
0.21±0.03
0.20±0.05
0.15±0.02
Mean Neointimal area, mm2
1.43 ± 0.36
2.11 ± 0.41
Mean flow area, mm2
7.02 ± 1.24
6.07 ± 1.39
5.99 ± 1.61
Minimal flow area, mm2
5.68 ± 1.24
4.66 ± 1.42
4.22 ± 1.37
Area stenosis obstruction, %
19.36 ± 7.51
24.12 ± 10.45
29.70 ± 11.14
Uncovered struts, %
2.04 ± 2.68
1.03 ± 1.84
Incomplete strut apposition, mm2
0.25 ± 0.45
(n=11)
0.22 ± 0.17
(n=5)
1.97
(n=1)
Scaffold enlargement !!
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< non-significant change, < P < 0.05
Values are expressed as mean ± SD
van Geuns, R. – ABSORB cohort B1 – 2 Yr OCT data, AHA 2011

26. Minimal scaffold area, mm² First signs of bioresorption
Results of Quantitative OCT Serial Analysis
OCT
Post procedure
(n=23)
6 month
24 month
BL-2Y
Mean scaffold area, mm2
7.47±1.18
7.70 ± 1.34
8.24 ± 1.83
Minimal scaffold area, mm²
6.22 ± 1.26
6.17 ± 1.46
6.36 ± 1.41
Mean Strut core area, mm2
0.21±0.03
0.20±0.05
0.15±0.02
Mean Neointimal area, mm2
1.43 ± 0.36
2.11 ± 0.41
Mean flow area, mm2
7.02 ± 1.24
6.07 ± 1.39
5.99 ± 1.61
Minimal flow area, mm2
5.68 ± 1.24
4.66 ± 1.42
4.22 ± 1.37
Area stenosis obstruction, %
19.36 ± 7.51
24.12 ± 10.45
29.70 ± 11.14
Uncovered struts, %
2.04 ± 2.68
1.03 ± 1.84
Incomplete strut apposition, mm2
0.25 ± 0.45
(n=11)
0.22 ± 0.17
(n=5)
1.97
(n=1)
<
<
< = = = =
>
>
First signs of bioresorption
<
>
>
>
>
>
>
>
>
<
<
<
< non-significant change, < P < 0.05
van Geuns, R. – ABSORB Cohort B1 – 2 Yr OCT data, AHA 2011
Values are expressed as mean ± SD

27. Minimal scaffold area, mm² Well controlled inhibition of neointima
Results of Quantitative OCT Serial Analysis
OCT
Post procedure
(n=23)
6 month
24 month
BL-2Y
Mean scaffold area, mm2
7.47±1.18
7.70 ± 1.34
8.24 ± 1.83
Minimal scaffold area, mm²
6.22 ± 1.26
6.17 ± 1.46
6.36 ± 1.41
Mean Strut core area, mm2
0.21±0.03
0.20±0.05
0.15±0.02
Mean Neointimal area, mm2
1.43 ± 0.36
2.11 ± 0.41
Mean flow area, mm2
7.02 ± 1.24
6.07 ± 1.39
5.99 ± 1.61
Minimal flow area, mm2
5.68 ± 1.24
4.66 ± 1.42
4.22 ± 1.37
Area stenosis obstruction, %
19.36 ± 7.51
24.12 ± 10.45
29.70 ± 11.14
Uncovered struts, %
2.04 ± 2.68
1.03 ± 1.84
Incomplete strut apposition, mm2
0.25 ± 0.45
(n=11)
0.22 ± 0.17
(n=5)
1.97
(n=1)
<
<
< = = = = =
>
>
<
Well controlled inhibition of neointima
>
>
>
>
>
>
>
>
<
<
<
< non-significant change, < P < 0.05
Values are expressed as mean ± SD
van Geuns, R. – ABSORB cohort B1 – 2 Yr OCT data, AHA 2011

28. Minimal scaffold area, mm² Minimal reduction in functional lumen area
Results of Quantitative OCT Serial Analysis
OCT
Post procedure
(n=23)
6 month
24 month
BL-2Y
Mean scaffold area, mm2
7.47±1.18
7.70 ± 1.34
8.24 ± 1.83
Minimal scaffold area, mm²
6.22 ± 1.26
6.17 ± 1.46
6.36 ± 1.41
Mean Strut core area, mm2
0.21±0.03
0.20±0.05
0.15±0.02
Mean Neointimal area, mm2
1.43 ± 0.36
2.11 ± 0.41
Mean flow area, mm2
7.02 ± 1.24
6.07 ± 1.39
5.99 ± 1.61
Minimal flow area, mm2
5.68 ± 1.24
4.66 ± 1.42
4.22 ± 1.37
Area stenosis obstruction, %
19.36 ± 7.51
24.12 ± 10.45
29.70 ± 11.14
Uncovered struts, %
2.04 ± 2.68
1.03 ± 1.84
Incomplete strut apposition, mm2
0.25 ± 0.45
(n=11)
0.22 ± 0.17
(n=5)
1.97
(n=1)
<
<
< = = = = =
>
>
<
>
>
>
Minimal reduction in functional lumen area
>
>
>
<
<
< non-significant change, < P < 0.05
Values are expressed as mean ± SD
van Geuns, R. – ABSORB cohort B1 – 2 Yr OCT data, AHA 2011

29. Minimal scaffold area, mm²
Results of Quantitative OCT Serial Analysis
OCT
Post procedure
(n=23)
6 month
24 month
BL-2Y
Mean scaffold area, mm2
7.47±1.18
7.70 ± 1.34
8.24 ± 1.83
Minimal scaffold area, mm²
6.22 ± 1.26
6.17 ± 1.46
6.36 ± 1.41
Mean Strut core area, mm2
0.21±0.03
0.20±0.05
0.15±0.02
Mean Neointimal area, mm2
1.43 ± 0.36
2.11 ± 0.41
Mean flow area, mm2
7.02 ± 1.24
6.07 ± 1.39
5.99 ± 1.61
Minimal flow area, mm2
5.68 ± 1.24
4.66 ± 1.42
4.22 ± 1.37
Area stenosis obstruction, %
19.36 ± 7.51
24.12 ± 10.45
29.70 ± 11.14
Uncovered struts, %
2.04 ± 2.68
1.03 ± 1.84
Incomplete strut apposition, mm2
0.25 ± 0.45
(n=11)
0.22 ± 0.17
(n=5)
1.97
(n=1)
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< = = = = = =
>
>
>
<
>
>
>
>
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<
Almost complete coverage of the struts with resolution of incomplete apposition
< non-significant change, < P < 0.05
Values are expressed as mean ± SD
van Geuns, R. – ABSORB cohort B1 – 2 Yr OCT data, AHA 2011

30. ABSORB EXTEND Non-Randomized, Single-Arm, Continued Access Trial
~1,000 subjects
Up to 100 global sites (non-US)
Clinical Follow-Up
Clinical Follow-up (months) 6 12 18 24 36
MSCT follow up (n=100)
OCT, IVUS follow up (n=50)
Study Objective
Continued Access trial. FPI: Jan 11, 2010
Endpoints
Typical PCI clinical endpoints
Treatment
Up to 2 de novo lesions in different epicardial vessels Planned overlapping allowed in lesions >22 and ≤ 28 mm
Device Sizes
Scaffold diameters: 2.5, 3.0, 3.5 mm Scaffold lengths: 12*, 18, 28 mm
Bartorelli, A, An Interim Report on the 12-Month Clinical Outcomes from the First 250 Patients Registered,
and An Interim Report on the 6-Month Clinical Outcomes from the First 500 Patients Registered, TCT 2012
12 mm lengths in 3.0 and 2.5 mm diameters will be introduced into trial
when available

31. Intent to Treat (ITT) Analysis – Interim Snapshot
ABSORB EXTEND: One Year Outcomes in 250 Patients MACE at 12 Months
Intent to Treat (ITT) Analysis – Interim Snapshot
Bartorelli, A, An Interim Report on the 12-Month Clinical Outcomes from the First 250 Patients Registered, TCT 2012

32. Intent to Treat (ITT) Analysis – Interim Snapshot
ABSORB EXTEND: One Year Outcomes in 250 Patients Ischemia-Driven TLR at 12 Months
Intent to Treat (ITT) Analysis – Interim Snapshot
Bartorelli, A, An Interim Report on the 12-Month Clinical Outcomes from the First 250 Patients Registered, TCT 2012

33. ABSORB Clinical Program: Summary
Current clinical data for the Absorb™ BVS have shown:
Safety and efficacy through 5 years (ABSORB Cohort A), through 2 years (ABSORB Cohort B), and through 1 year (EXTEND, interim 250 pts)
No ST in ABSORB Cohort A1 and Cohort B3; low ST ABSORB EXTEND4
No new MACE from 6 months to 5 years (Cohort A) and between 1 and 3 years in ABSORB Cohort B
Imaging data shows
Possible restoration of vasomotor function by angio2
Late scaffold enlargement by OCT1
Resorption of Absorb™ has been shown on OCT, with the final golden tube at long-term follow-up* (5 Years, Cohort A)
1Serruys, PW., TCT 2011; 2 J. Ormiston, TCT 2011; 3 D. Dudek, ABSORB Cohort B Trial, Evaluation of the Absorb Everolimus Eluting Bioresorbable Vascular Scaffold (Absorb BVS) in the Treatment of Patients with de novo Native Coronary Artery Lesions, 2-Year Clinical Results, ACC 2012 ; 4 Bartorelli, A, An Interim Report on the 12-Month Clinical Outcomes from the First 250 Patients Registered, and An Interim Report on the 6-Month Clinical Outcomes from the First 500 Patients Registered, TCT 2012
* Ongoing trial outside of the United States
* Thoraxcenter, Erasmus MC, Rotterdam, The Netherlands, ABSORB A 5 yr