1. DESSOLVE Clinical Trial Program
MiStent® Sirolimus-Eluting Absorbable Polymer Coronary Stent System (MiStent SESTM)
Dennis Donohoe, MD

2. Disclosures Chief Medical Advisor for Micell Technologies
Consultant to other companies developing coronary and peripheral vascular devices
The MiStent SES is an investigational device that is not approved and is not available for sale in any country.
Micell, Micell Technologies, the Micell Logo, MiStent and
MiStent SES are among the trademarks of Micell Technologies, Inc.

3. Clinical Issues Related to Durable Polymers
Late DES failure of safety and efficacy has been attributed to durable polymers:
Stimulus for chronic inflammation
Localized hypersensitivity reactions
Incomplete re-endothelialization
Positive remodeling
Acquired incomplete stent apposition
Neoatheroma formation
Cook, et al. Circulation. 2009;120: ; Joner, et al. J Am Coll Cardiol. 2006;48:193–202; Cook, et al.. Circulation. 2007;115:

4. MiStent SES Absorbable Polymer System
Designed with known components combined using a proprietary process for improved safety and differentiated performance
Polymer – PLGA
Cleared from the stent in days leaving a BMS
Polymer eliminated from tissue in 90 days
Drug – SIROLIMUS
Crystalline form (provides for sustained drug release)
Extensively tested and proven drug
Highly effective for suppression of NIH
Stent and Delivery System
Stent – GENIUS® Magic Stent and Rx Catheter
Thin strut (64µm) cobalt chromium coronary stent with CE Mark
Flexible and trackable with visibility and accuracy

5. DESSOLVE Clinical Trial Program
DESSOLVE I
First-in-Human, 30 patients, 5 sites
Mechanistic design to investigate neointimal proliferation & vessel healing
4,6,8 month data - Angiography, IVUS, OCT
DESSOLVE II
RCT with 2:1 randomization with Endeavor Sprint®
184 patients at 26 sites
Primary Efficacy Endpoint: Superiority of In-stent LLL at 9 months
Primary Safety Endpoint: Non-inferiority of MACE (death, MI, TVR)
9 month – Angiography – with OCT, EFT, subgroup evaluations
All patients followed to 12 months

6. DESSOLVE I & II Enrollment Criteria Patient: Target Lesion:
Stable or unstable angina pectoris (Class I, II, III or IV), documented ischemia, or documented silent ischemia
No recent MI (<72 hrs) or elevated cardiac biomarkers
Target Lesion:
Planned single*, de novo, types A, B1 or B2 coronary lesions in a native coronary artery with >50% diameter stenosis
Vessel diameter and lesion length suitable for mm x 9-30 mm stent
Exclusion if highly calcified, tortuous, thrombus present, proximal angulation
Exclusion if located at side branch >2.5mm, ostial location, previously treated vessel
*Treatment of a non-target vessel lesion permissible before target lesion PCI if no procedural complications

7. DESSOLVE Investigational Sites
STUDY PRINCIPAL INVESTIGATORS: William Wijns, MD, PhD
John Ormiston, MB ChB
Study Sites
Belgium
Genk - Mathias Vrolix*
Antwerp - Stefan Verheye
Brussels - Danny Schoors
Aalst - William Wijns*
Leuven - Walter Desmet
Hasselt - Edouard Benit
The Netherlands
Amsterdam - Ton Slagboom
Zwolle – Marcel Gosselink
Nieuwegein - Maarten Jan Suttorp
Utrecht - Pieter Stella
Tilburg - Wilbert Aarnoudse
France
Massy - Marie-Claude Morice
Toulouse - Jean Fajadet
Quincy - Philippe Garot
New Zealand
Christchurch - Dougal McClean
Mercy - John Ormiston*
Auckland - Jim Stewart*
Wellington - Scott Harding
United Kingdom
Manchester - Saqib Chowdhary
London - Carlo DiMario
Southampton - Iain Simpson
Norwich - Alisdair Ryding
Cambridge - Cameron Densem
Brighton - David Hildick-Smith
Sweden
Orebro - Leszek Zagozdzon
Gothenberg - Per Albertsson
Australia
Melbourne - Robert Whitbourn*
Core Labs
Angiography – Yale – Alexandra Lansky
IVUS – Stanford – Peter Fitzgerald
OCT – Case Western – Hiram Bezerra, Marco Costa
Data Management, Safety and Monitoring
Harvard Clinical Research Institute (HCRI)
Genae Associates
Pacific Clinical Research Group (PCRG)
*DESSOLVE I sites

8. DESSOLVE I 2010/11 2016 Study Design and Patient Allocation
2010/
PROCEDURE
30D 4M 6M 8M
12M
18M
2-5Y
4M (n=10)
Angio, IVUS, OCT
Clinical
2,3,4,5Y
Long-term
Clinical
Follow-up
Enrolled (n=30)
12M (n=30)
Clinical
Follow-Up
18M (n=30)
Angio, IVUS, OCT
Clinical
6M (n=10)
Angio, IVUS, OCT
Clinical
8M (n=10)
Angio, IVUS, OCT, Clinical
27 imaging
3 clinical only due to health status
29 patients completed
2 year follow-up

9. DESSOLVE I Outcomes Procedure MiStent SES (N=30) Clinical@ 2 Years
Lesion Success
100%
Device Success
96.6% (n=29)1
Procedural Success
1 MiStent SES was unable to cross the lesion due to calcification in the artery - a subsequent MiStent was successfully implanted
2 Years
MiStent SES (N=30)
MACE2
3.3% (n=1)3
Stent Thrombosis 0%
2 MACE defined as death, MI (QWMI and NQWMI) and TVR
3 Non TV, NQWMI: increased troponin following diagnostic angiogram at 44 days post-index procedure

10. No evidence of progression of LLL from 8 month to 18 month follow-up
DESSOLVE I
18M Imaging
No evidence of progression of LLL from 8 month to 18 month follow-up
Angiography
Neointimal Obstruction
IVUS
Late Lumen Loss (mm)
Data represents cases that returned at 18M within the study window (±30days) and had paired imaging available from 4,6,8 month follow-up visit.

11. DESSOLVE I
18M Imaging
OCT shows a high rate of strut coverage at all time points with no acquired incomplete stent apposition
% Stent Strut Coverage
mean median
4 Month
6 Month
8 Month
18 Month
OCT
Neointimal Hyperplasia/Thickness(µm)
Data (means) represents cases evaluated by OCT core lab at each follow-up visit
(4M n=10, 6M n=9, 8M n=9, 18M n=25)

12. DESSOLVE II 2011 2016 Study Design and Patient Allocation
PROCEDURE
30D 6M 9M
12M
2-5Y
MiStent SES
N=121
MiStent SES – 9M
N=117, 97%
(103 angio)
12M
Clinical Follow-Up
N=176, 97%
(2 death, 3 LTFU)
Randomized
2:1
N=184 ITT*
N=181 PP
2,3,4,5Y
Long-term
Clinical
Follow-up
Endeavor
N=60 PP
Endeavor – 9M
N=59, 98%
(52 angio)
*3 patients
non-study stents implanted
at target lesion
All available patients contacted for
12 month follow-up

13. DESSOLVE II Baseline Clinical Characteristics Variable MiStent SES
Endeavor
(N=60)
P Value
Age (mean ± SD)
64.9 ± 10.5
65.0 ± 10.5
0.956
Male
69.4
75.0
0.488 MI
23.5
16.7
0.337
Previous PCI of Target Vessel
3.3
5.0
0.687
CABG
4.2
1.000
Diabetes Mellitus
18.5
20.0
0.841
Hypertension
70.8
68.3
0.733
Hypercholesterolemia
73.1
83.1
0.189
Current Smoker
21.8
25.4
0.696
Angina Status Stable
Unstable
Silent Ischemia
78.5
14.9
6.6
79.7
13.6
6.8
0.973
Data expressed as mean ± SD or percent

14. DESSOLVE II Baseline Angiographic Characteristics Measure MiStent SES
(Lesions=121)
Endeavor
(Lesions=60)
P Value
Vessel Location LAD
LCX
RCA
43.8
21.5
34.7
36.7
38.3
25.0
0.053
Lesion Location Proximal
Mid
Distal
35.5
47.9
15.7
46.7
13.3
0.478
Lesion Length <10 mm
10-20 mm
>20 mm
27.3
64.5
8.3
31.7
56.7
11.7
0.843
Calcification Moderate-Severe
0.602
TIMI Flow 3
91.7
0.987
Lesion Classification A B1
B2/C
46.3
45.5
10.0
45.0
0.991
Data expressed as percent

15. DESSOLVE II Procedural QCA Results Measure MiStent SES Endeavor DES
Mean ± SD
Endeavor DES
P Value
Pre-Procedure
Lesion Length (mm)
13.46 ± 4.82
13.51 ± 6.21
0.96
RVD (mm)
2.87 ± 0.38
2.83 ± 0.42
0.51
MLD (mm)
0.83 ± 0.22
0.81 ± 0.29
0.57
% Stenosis
70.71 ± 7.80
71.35 ± 9.40
0.63
Post-Procedure
2.94 ± 0.38
2.85 ± 0.44
0.15
In-Stent MLD (mm)
2.83 ± 0.34
2.86 ± 0.38
0.69
In-Stent %DS
3.38 ± 7.29
-0.72 ± 7.19
<0.001
In-Lesion %DS
13.42 ± 7.61
14.13 ± 6.84
0.54

16. DESSOLVE II Procedural Outcomes Measure MiStent SES Endeavor DES
Lesion Success
100%
Device Success
Procedural Success
98.3%
96.7%
P=NS for all comparisons

17. DESSOLVE II Primary Efficacy Endpoint: 9 Month In-stent Late Loss
Late Lumen Loss (mm)
N=103
N=52
MiStent SES
Endeavor ZES
Data expressed as mean ± SD

18. DESSOLVE II 9 Month Angiographic Outcomes Variable MiStent SES
Mean or % (N)
MiStent SES
(N=103)
Endeavor ZES
(N=52)
P Value
In-Stent MLD (mm)
2.58 ± 0.53
2.28 ± 0.51
0.001
In-Stent % DS
12.11 ± 16.10
19.34 ± 15.62
0.008
Late Loss In-Lesion (mm)
0.19 ± 0.43
0.34 ± 0.36
0.029
% In-Stent Binary Restenosis
4.9 (5)
1.9 (1)
0.66
% In-Lesion Binary Restenosis
3.8 (2)
1.00
Data expressed as mean ± SD or percent (N)

19. DESSOLVE II Primary Safety Endpoint: 9 Month MACE P=0.49 Percent
Note: 9-Month DAPT adherence 85% for each cohort

20. DESSOLVE II 9 Month OCT Results Measure MiStent SES Endeavor ZES
% Uncovered Struts
Max Segment Length with Uncovered Strut (mm)
0.34
0.60
0.00
% Strut Malapposition
Max Segment Length with Malapposed Struts (mm)
Data expressed as median or percent (N)

21. DESSOLVE II 9 Month Endothelial Function by Rapid Atrial Pacing
EFT Status
MiStent SES
Endeavor ZES
Responders
100% (19/19)
90% (9/10)
Non-Responders
0% (0/19)
10% (1/10)
Vasoconstrictors
0% (0/10)
Need P values and a caption defining what a responder, non-responder and vasoconstrictor is
P=NS for all comparisons
Vasomotor Response
Responder: Dilation of the proximal/distal reference vessel segment after pacing indicating normal endothelial function
Non-responder: No dilation or constriction of the proximal/distal reference vessel segment after pacing indicating abnormal endothelium throughout the vessel
Vasoconstrictor: Constriction of the proximal/distal reference vessel segment after pacing indicating endothelial dysfunction

22. MiStent DESSOLVE Clinical Trial Program
Summary
DESSOLVE I
Stability in luminal dimensions through 18 months by angiographic and IVUS imaging; OCT confirming uniform strut coverage with no acquired malapposition
DESSOLVE II
Angiographic: Superior MiStent SES performance against the primary endpoint of in-stent LLL
Clinical: 9 months TLR 0.9% and MACE 4.3% with no def/probable ST
OCT: High uniformity of NIH distribution over length of stent with 0.34% strut coverage and 0% malapposition through 9 months
EFT: Maintenance of endothelial function at 9 months with vasodilation