1. The OrbusNeich EPC Capture Biodegradable Polymer Sirolimus-eluting Stent Program Michael JB Kutryk, MD, PhD St Michael’s Hospital, Toronto

2. Michael JB Kutryk, MD, PhD
Consultant
ORBUS- NEICH.

4. Combo Bio-engineered Sirolimus Eluting Stent
Designed to combine
the pro-healing EPC capture technology found in the Genous™ Bio-engineered R stent™ for rapidly achieving endothelial coverage
abluminal sirolimus sustained drug elution for the control of neointimal proliferation. 4 4

5. Applying EPC Capture Technology to DES
Genous
3 Days
14 Days
CD34/Cypher
Cypher
Nakazawa G et al., JACC Cardiovasc Interv Jan;3(1):68-75.

6. % of Endothelial Cells Expressing PECAM
Control
Control
AbC 25 50 75
(70.5)
(27.7)
3 Days
14 Days
% PECAM
P= 0.07
Antibody coated
P=0.07
Courtesy of Renu Virmani, MD 6

7. Can the compatibility be improved by abluminal coating?
Control
Abluminal
Coating

9. Porcine Coronary Model at 14 and 28 Days
Objective:
To demonstrate the effect of sirolimus dose on healing (anti-CD34 effect) and reduction of neointimal proliferation (sirolimus effect)
Test Devices:
Combo ¼ Dose/Low Dose (LD) = 2.5 µg sirolimus/mm, n= 5
Combo ½ Dose/Half Dose (HD) = 5 µg sirolimus/mm, n= 5
Cypher, Xience V, Genous
Endpoints:
14 days:
SEM & IMH (4 stents in each HD and LD)
In vivo OCT evaluation: (4 in each group)
28 days: OCT & LM (6 stents in Genous, HD and LD, 4 stents in DES controls)
IMH=immunohistochemistry with PECAM (anti-CD31) staining and confocal microscopy; LM=light microscopy
Courtesy of Juan Granada, MD, Skirball Center for Cardiovascular Research/CRF

10. Endothelial Expression of PECAM at 28 d
Mean % Endothelial Coverage was calculated by determining the percent coverage (by SEM) that was also positive for PECAM expression
Courtesy of Juan Granada, MD, Skirball Center for Cardiovascular Research/CRF

11. 28 Days OCT Images (Porcine Study)
Combo Stent: Accelerated Healing with Control of Neointima
28 Days OCT Images (Porcine Study)
Combo
Genous
Cypher
Xience V
Courtesy of Juan Granada, MD, Skirball Center for Cardiovascular Research/CRF

12. Neointimal Formation Evaluation
HD had the lowest degree of neointimal thickness, (0.173±0.088mm) compared to Cypher (0.358± 0.225mm) LD (0.316±0.228mm), Genous (0.300±0.156mm) and Xience (0.305±0.252mm); p< for all pairwise comparisons to HD
Courtesy of Juan Granada, MD, Skirball Center for Cardiovascular Research/CRF

13. *Cypher>Xience and HD; **Xience>Genous, HD and LD (p<0.0001)
28 Day Histology Results
Genous
n=6
Cypher
n=3
Half Dose
n=5
Low Dose
Xience
Stenosis (%)
36.55±10.88
33.48±5.41*
19.92±5.60
26.04±8.74
22.22±6.27
NI Thickness (mm)
0.29±0.12
0.21±0.019
0.12±0.050
0.18±0.073
0.15±0.049
Fibrin Score
0.067±0.16
2.00±0.72
0.60±0.75
1.32±0.50
0.53±0.42
Int. Inflam. Score
0.27±0.16
1.20±0.20
0.28±0.23
0.24±0.33
0.67±0.83
Giant Cells (%)
13.82±9.51
44.94±8.32
10.06±7.13
6.04±7.55
33.24±14.14**
*Cypher>Xience and HD; **Xience>Genous, HD and LD (p<0.0001)
Courtesy of Juan Granda, MD and Renu Virmani, MD

14. Summary
In pre-clinical studies, the OrbusNeich Bio-engineered Sirolimus Eluting Stent (Combo Stent) demonstrated
significantly lower neointimal hyperplasia
improved endothelial coverage relative to other commercially available DES
lower presence of inflammation and foreign body reaction
appeared effective at inhibition of neointimal growth while enhancing endothelial coverage
potentially resulting in low rates of in-stent restenosis comparable to commercially available DES and in reduced rates of late stent thrombosis
Favorable preclinical data prompted initiation of the REMEDEE clinical trial 14 14

15. Randomized Evaluation of an abluMinal sirolimus coatED bio-Engineered stEnt

16. Combo Bio-engineered Sirolimus Eluting Stent
Granada J et al., CIRC Cardiovasc Interv, June 2010; 3

17. Drug Elution Drug – Sirolimus
Polymer - biodegradable Surmodics SynBiosys™
Drug content is 5 µg/mm stent length, approximately half the dose of CYPHER™ but with a similar release profile 20 40 60 80
100
0.25 1 3 7 14 28 35
Time (days)
% Elution over time
Combo
Cypher
In vitro elution of Combo and CYPHER® (% of total drug eluted over time) 17 17

18. REMEDEE Study Design
Prospective, multicenter, randomized study (n=180)
16 investigational sites in Europe, Australia, Asia, and South America
Randomized 2:1 to the Combo Stent vs. TAXUS® Liberté®
≥ 2.5 mm and ≤ 3.5 mm (lesion length ≤ 20 mm)
Dual anti-platelet therapy for 6 months
Primary end-point: In-stent late lumen loss of the Combo Stent compared to the TAXUS Liberté DES at 9 months post procedure
Principal Investigators: A. Abizaid, M. Haude, I. Meredith, S. Windecker 18 18

19. REMEDEE Enrollment (n=183)

20. REMEDEE Timeline Last Patient Enrolled August 2010
Complete 9m Follow Up Q2 2011
Final Report Q3 2011
Data for Presentation Q4 2011 20

21. THANK YOU 21 21