1. Elixir Medical Novolimus Elution from A Biodegradable Polymer
CRT 2012
Elixir Medical Novolimus Elution from A Biodegradable Polymer
Alexandre Abizaid, MD, PhD
On behalf of the EXCELLA BD Investigators
International (OUS) Use Only

2. Alexandre Abizaid, MD, PhD
Consulting Fees:
Abbott Vascular
BSC

3. Innovating Vascular Restoration
Pharmacological Agent
Limus Family
↓ Drug dose
↑ Spatial distribution
↑ Residual tissue conc.
Controlled Release
Biocompatible Polymers
Durable
Bioabsorbable
↓ Polymer load
Stent Platform
Cobalt Chromium Alloy
↓ Strut thickness
↑ Flexibility & Deliverability
↑ Vessel coverage
Stent Scaffold
Fully bioresorbable
↑ Sustained clinical performance
↑ Vasomotion

4. Novolimus known safety profile
Active metabolite of Sirolimus
Binds to FKBP12 forming an immunosuppressive complex
mTOR inhibitor
Known Safety Profile
Patients treated with Sirolimus orally or via DES implantation exposed to significant amount of Novolimus
Potent anti-proliferative
Inhibition of proliferation of hSMC IC50 = 0.5nM
Formula:
C50H77NO13
MW: 900
Drug Concentration 
Systemic Novolimus Exposure after oral Sirolimus
Elixir Novolimus DES & Scaffold
Not to scale
Oral Sirolimus
Sustained performance with low drug dose
(5 ug/mm stent length for all product platforms)
Time 

5. Controlled Release Technology DESyneTM (Durable Polymer) and DESyne BDTM (Biodegradable Polymer)
DESyne and DESyne BD
Cypher
Xience / Promus
Resolute
BioMatrix
Synergy
Strut Thickness (µm)
Polymer Thickness (µm)
Drug Load (µg) 5

6. DESyne™ and DESyne BDTM Novolimus-eluting DES Features
DESyneTM
Durable polymer drug release over 12 weeks
Workhorse DES with sustained clinical performance through 2 years
Platform features
Cobalt chromium alloy stent
81 µm thickness
Novolimus drug dose of 5 mcg per mm stent length
Thin polymer matrix
No primer coating
< 3µm coating thickness
DESyne BDTM
Biodegradable polymer degrades in 6-9 months, drug release over 4 weeks
Workhorse DES that leaves behind bare metal surface

7. Elixir clinical programs running in parallel across three platforms
Pharmaceutical
Novolimus
Products
DESyneTM
DESolveTM
FIM
completed*
DESyneTM BD
FIM
completed
FIM
completed
FIMs CE
Studies
EXCELLA II
RCT
Completed
EXCELLA BD
RCT
Completed
DESolve Nx
Enrollment
Ongoing
IDE
Studies
EXCELLA III
Pending
*Myolimus

8. EXCELLA II Randomized Clinical Trial
RANDOMIZED (2:1), SINGLE BLIND, MULTI-CENTER CLINICAL TRIAL
Principal Investigator: P. W. Serruys, MD, PhD
Co-Principal Investigators:
A. Abizaid, J.Ormiston
Angiographic Core Lab: Cardialysis
IVUS Core Lab: Stanford University
CEC/DSMB: Cardialysis
Data Management: Cardialysis
Single/Multiple De Novo Native Coronary Artery Lesions (A-B2)
Vessel Diameters: mm
Stent Diameters: mm
Lesion Length: ≤24 mm
Stent Lengths: mm
Pre-Dilatation required / Post-Dilatation at physicians discretion
Cobalt Alloy Stent + Durable Polymer + 5µg per mm Stent Length
ENDEAVOR DES Control
n= 71
Geography: New Zealand, Australia, Europe and Brazil
EXCELLA DES
n= 139
30d mo mo mo yrs
Clinical Follow-up
Angiographic/IVUS (Subset) Follow-up
Clinical Follow-up
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Primary Endpoint: In-Stent Late Lumen Loss at 9 months (QCA)
Device and Procedure (Clinical) Success
Device-oriented composite endpoint (Death, MI, or TLR)
Key Secondary Endpoints: at 1, 6, 9, 12mo and 2-5 yrs
Clinically driven TLR, TVR and TVF at 1, 6, 9, 12mo and 2-5 yrs
Stent thrombosis rates at 1, 6, 9, 12mo and 2-5yrs
ABR, LLL and % volume obstruction at 9 months
Anti-Platelet Therapy for 12 months 8

9. Angiographic and IVUS Results 9 months
In-Stent Analysis
Novolimus
Zotarolimus
P value
RVD (mm)
N(L)=154
N(L)= 75
Post-procedure
2.84±0.43
2.91±0.38
0.20
At 9-months
2.82±0.44
2.70±0.42
0.06
MLD / Late Lumen loss (LLL), (mm)
Acute gain
1.36±0.40
1.47±0.36
0.047
Acute gain (%)
46.48±11.65
47.51±11.13
0.53
MLD post-procedure
2.48±0.39
2.57±0.37
0.10
MLD at 9-months
2.36±0.48
1.95±0.48
< 0.001
LLL at 9-months
0.11±0.32
0.63±0.42
Diameter Stenosis (%)
12±5
11±5
0.34
16±12
28±14
Binary Restenosis (%)
1.4% (2/138)
7.6% (5/66)
0.037
Volumetric Analysis
N(L)=34
N(L)=15
%Neointimal volume obstruction (%)
4.5±5.1
20.9±11.3
<0.001

10. EXCELLA II Randomized Clinical Trial
Cardiac Events at 1 and 2 years
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11. EXCELLA BD Randomized Clinical Trial
RANDOMIZED (3:1), SINGLE BLIND, MULTI-CENTER CLINICAL TRIAL
Co-Principal Investigators:
A. Abizaid and S. Verheye
Angiographic Core Lab: CRC
IVUS Core Lab: Stanford University
CEC/DSMB: CRC
Data Management: CRC
Single/Multiple De Novo Native Coronary Artery Lesions (A-B2)
Vessel Diameters: mm
Stent Diameters: mm
Lesion Length: ≤24 mm
Stent Lengths: mm
Pre-Dilatation required / Post-Dilatation at physicians discretion
Cobalt Alloy Stent + Bioabsorbable Polymer + 5µg per mm Stent Length
ENDEAVOR DES Control
n= 31
Geography: Belgium, Germany and Brazil
DESyne BD DES
n= 115
Clinical Follow-up
Angiographic/IVUS (Subset) Follow-up
30d mo mo mo yrs
Primary Endpoint: In-Stent Late Lumen Loss at 6 months (QCA)
Device and Procedure (Clinical) Success
Device-oriented composite endpoint (Death, MI, or TLR)
Key Secondary Endpoints: at 1, 6, 9, 12mo and 2-5 yrs
Clinically driven TLR, TVR and TVF at 1, 6, 9, 12mo and 2-5 yrs
Stent thrombosis rates at 1, 6, 9, 12mo and 2-5yrs
ABR, LLL and % volume obstruction at 6 months
Anti-Platelet Therapy for 12 months
Clinical Follow-up
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12. Patient Flow and Follow-up
151 patients (NL=168)
enrolled and randomized
1 Deregistered
3 Withdrew consent
3 no study stent
1 Deregistered
Novolimus-eluting stent
N=115 pts (NL=127)
Zotarolimus-eluting stent
N=31 pts (NL=38)
30-day clinical FUP
N=115 pts
9-month clinical FUP
N=31 pts
Clinical FUP 100%
6-month clinical FUP
N=113 pts
6-month clinical FUP
N=31 pts
Clinical FUP 98.6%
6-month angio FUP
N=107 pts
(NL= 119) (NIVUS = 35)
6-month angio FUP
N=31 pts
(NL= 38) (NIVUS = 16)
Angio FUP 94.5%
Intention to treat analysis
Pts, patients; NL number of lesions; NIVUS number of IVUS

13. Baseline Patient Characteristics
% (n) unless stated
DESyne BD
(N=115 patients)
ZES
(N=31 patients)
Age, years (± SD)
65.0±9.3
60.4±10*
Male
63.5%
77.4%
Diabetes mellitus
28.7%
25.8%
Current Smoker
18.3%
29.0%
Hypercholesterolemia
72.2%
80.7%
Hypertension
80.9%
Previous myocardial infarction
25.2%
32.3%
Previous CABG
5.2%
0.0%
Previous PCI
20.0%
Unstable angina
10.4%
9.7%
*p=0.028; all others p=ns

14. Angiographic Results 6 months
In-Stent Analysis
Novolimus
Zotarolimus
P value
RVD. mm
N(L)=119
N(L)= 38
Post-procedure
3.00±0.37
3.08±0.35
0.31
At 6-months
2.95±0.37
2.99±0.38
0.67
MLD / Late Lumen loss (LLL), (mm)
Acute gain
1.87±0.42
2.01±0.43
0.09
MLD post-procedure
2.76±0.37
2.90±0.34
0.04
MLD at 6-months
2.64±0.39
2.22±0.53
<0.001
LLL at 6-months (in-stent)
0.12±0.15
0.67±0.47
< 0.001
Diameter Stenosis (%)
8.5±44
6.2±4.5
0.002
11.0±6.6
25.6±15.1
Binary Restenosis (%) (in-stent)
0.0%
7.9%
0.003

15. Primary Endpoint Analysis: 6-month In-Stent Late Lumen Loss
Novolimus
0.12
Zotarolimus
0.67
DELTA*
(Upper 1-sided 95% CI)
-0.55 (-0.44)
Non-inferiority
P value
<0.001
Superiority
*Least square means
Zone of non-inferiority
Pre-specified margin=0.20mm
Zone of Superiority
Zone of non-inferiority
Zone of inferiority
Superior
-0.60
-0.50
-0.40
-0.30
-0.20
-0.10
0.00
0.10
0.20
0.30
0.40
Upper one-sided 95% CI
Met Primary Non-Inferiority Endpoint and Superiority Endpoint

16. DESyne BDTM Neointimal Obstruction
Optimal neointimal coverage with low neointimal volume obstruction
Neointimal volume obstruction by IVUS at 6 months (%)
4-6 month results for similar trials* TM TM TM TM
4-8 month results for similar trials*
*ResoluteTM from RESOLUTE at 4m, Xience VTM from SPIRIT II at 6m except SPIRIT III at 8m for neointima free ratio (not available from SPIRIT II), Biomatrix from STEALTH at 6m, Synergy from EVOLVE at 6m (IVUS results not available)

17. Clinical Results – 6 months
0 to 270 days, % (n)
DESyne (N=112)
Endeavor
(N= 31)
P-Value
HIERARCHICAL EVENTS
DEVICE ORIENTATED COMPOSITE
2.7%
3.2%
1.00
CARDIAC DEATH
0.0% --
TARGET VESSEL MI
0.9%
        Q-WAVE MI
        NON-Q- WAVE MI
CLINICALLY-INDICATED TLR
1.8%
0.52
CI-PCI
CI-CABG
Modified Intention to Treat (patients who received a study stent)

18. Stent Thrombosis per ARC
0 to 180 days, % (n)
DESyne BD (N=115)
ZES
(N= 31)
P-Value
Definite Stent Thrombosis
0.0% -
Probable Stent Thrombosis

19. Conclusions
The EXCELLA BD Trial demonstrated both non-inferiority and superiority of the Elixir DESyne BD Novolimus eluting stent compared to the control Zotarolimus eluting stent for the primary endpoint of in-stent late lumen loss at 6 months
Angiographic binary restenosis for the DESyne BD stent was significantly lower compared to the control stent (0.0% vs. 7.9%, p=0.003)
The Elixir DESyne BD Stent demonstrated significantly greater inhibition of neointimal hyperplasia and uniform coverage measured by IVUS compared to the control
Device-oriented composite endpoints (cardiac death, MI and TLR) out to 6 months were similar between both groups demonstrating clinical safety of the Elixir DESyne BD stent
There were no reported stent thromboses through 6 months for either study group

21. Comparison of Event Rates
Significant reduction
p=0.045