1. MiStent SES® Program Technology and Clinical Data Update
David Kandzari, MD
Monday, February 22
11:41-11:48 pm

2. Affiliation/Financial Relationship Company
Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below
Affiliation/Financial Relationship Company
Grant/Research Support Abbott Vascular, Boston Scientific, Medtronic CardioVascular, Biotronik, Thoratec
Consulting Fees/Honoraria Boston Scientific Corporation, Medtronic CardioVascular, Micell
Major Stock Shareholder/Equity None
Royalty Income None
Ownership/Founder None
Intellectual Property Rights None
Other Financial Benefit None

3. REDEFINING DES – CRYSTALLINE SIROLIMUS WITH A RAPIDLY ABSORBED POLYMER COATING
MiStent Crystalline Sirolimus
Unique to MiStent SES, the sirolimus is maintained in a micro-crystalline morphology for controlled and prolonged elution, as opposed to use of an amorphous, rapid-release form of the drug.
MiStent Thin-Strut Stent
Cobalt-chromium
Highly deliverable (64 microns)
Reference: Carlyle et al, JCR 162 (2012) 561–567.

4. MISTENT SES: COMPARATIVE STRUT THICKNESS
Strut Thickness (µm)
BVS
150µm
BioMatrix
Flex
120µm
Resolute
Integrity
89µm
PROMUS
Element 81µm
XIENCE V
81µm
SYNERGY 74µm
MiStent 64µm
Adapted from K. Dawkins, CRT 2013.
Thinner struts are associated with more rapid healing and lower risk of acute thrombogenicity
Kolandaivelu, K., et al. Circulation 2011, 123(13),

5. DRUG DELIVERY VS POLYMER DISSOLUTION
MiStent SES – Crystalline drug presence in the tissue after elimination of polymer
Minimizes duration of inflammatory effect of polymer
Retains anti-restenotic drug for 3X longer than polymer is present
References: Carlyle et al, JCR 162 (2012) 561–567.
Adapted from Dawkins TCT2014 & product websites

6. UNIQUE MECHANISM OF DRUG DELIVERY
Crystalline sirolimus provides sustained elution to limit disease progression
Controlled drug release from moment of deployment
MiStent SES
An initial uncontrolled burst of drug may delay re-endothelialisation and coverage of the stent struts1
1 Deconinck E, et al. Pharmaceutical Aspects of Drug Eluting Stents. Journal of Pharmaceutical Sciences, 97(12), (2008).

7. DESSOLVE I: STUDY DESIGN
First-in-Human, 30 patients, 5 sites
PROCEDURE
30D 4M 6M 8M
12M
18M 2Y 3Y 4Y 5Y
4M (n=10)
Angio, IVUS, OCT
6M (n=10)
8M (n=10)
8M (n=30)
Clinical
12M
(n=30)
Clinical
Follow-Up
(n=27)
Angio,
IVUS, OCT
18M
2, 3, 4, 5Y
Long-term
Clinical
Follow-up
Enrolled (n=30)
5 sites
Mechanistic design to investigate quality of vessel healing
4, 6, 8-month data - angiography, IVUS, OCT
18-month data - angiography, IVUS, OCT
4-Year Completed
Ormiston, J., et al. (2013). JACC Cl 6 (10),

8. DESSOLVE I: SAFETY AT 4 YEARS
No Target Lesion Failure
No Target Lesion Related MACE
1 MI – Non-Target Vessel NQW-MI at 44 days
1 MI – Non-Target Vessel NQW-MI at 732 days
1 TVR at 1280 days
No Stent Thrombosis
MACE
TLF
1 year
3.3% (1/30)
0% (0/30)
2 years
3.4% (1/29)
0% (0/29)
3 years
6.9% (2/29)
4 years
10.3% (3/29)

9. DESSOLVE I: IMAGING RESULTS
Healing demonstrated by OCT through 18 months
OCT Results
Imaging with OCT demonstrated thin, homogeneous coverage with high rates of stent strut coverage at months
No evidence of definite neoatherosclerosis at 18 months
Thin homogeneous tissue coverage
Median
4-Month Group
6-Month Group
8-Month Group
18-Month Group
% Strut Coverage
93%
97%
96%
100%
References: Ormiston J, et al. JACC CI 2013
Attizzani G, et al. Am J Card 2013

10. DESSOLVE II: STUDY DESIGN
2:1 RCT design for superiority of in-stent LLL at 9 months with Endeavor
184 patients at 26 sites
PROCEDURE
30D 6M 9M
12M 2Y 3Y 4Y 5Y
2:1 RCT
26 sites
MiStent SES
n=123
Endeavor
n=61
9M - MiStent SES
Angio, OCT, EFT, Clinical
12M
n=175
Clinical
Follow-Up
2, 3, 4, 5Y
Long-term
Clinical
Follow-up
9M - Endeavor
Angio, OCT, EFT, Clinical
MiStent SES LLL was significantly lower than Endeavor at 9 months
4-Year Completed
0.27 ± 0.46 vs
0.58 ± 0.41
P<0.001
Wijns W et al. EuroInterv 2015;10:

11. DESSOLVE II: 4-Year Clinical Outcomes
P=0.27
P=1.00
P=0.72
P=0.18
P=1.00
P=0.31
P=0.33

12. ABSENCE OF LLL CATCH-UP TRANSLATES TO LOW TLR PROGRESSION
No Progression of In-stent Late Lumen Loss From 6/8 to 18 Months Follow Up
Results in low progression of target lesion revascularization (TLR) at 4 Years
CD-TLR Over Time
Angiography In-Stent Late Lumen Loss
N=152
Ormiston, J., et al. (2013). JACC Cl 6 (10),
Data on file - Micell

13. Comparison of Late-Term TLR with EES
Lansky, Byrne, et al. EuroPCR 2015

14. ONGOING CLINICAL STUDIES
Building on the success of the DESSOLVE I and II studies, three additional studies initiated in 2015
China Approval Study
RCT vs Tivoli DES
N = 400 pts
9-Month LLL, 12-Month TLF
Initiated Q2 2015
DESSOLVE III Study
Post-Marketing RCT vs Xience
N = 1400 pts
12-Month TLF
Enrollment completed 12/2015
DESSOLVE III Sub-Study
OCT RCT Sub-Study
N = 60 pts
Superiority for progression of NIH over time
Initiation Q4 2015

15. SUMMARY OF MISTENT PERFORMANCE
MiStent converts to a BMS in days and all polymer is absorbed in 90 days
Therapeutic levels of sirolimus in tissue is maintained beyond the polymer absorption due to use of crystalline drug
4-year pooled DESSOLVE I and II CD-TLR rate is 2.7%
No probable or definite ST through 4 years
MiStent has no late catch-up resulting in a low progression of TLR over long-term follow-up
potential for significant health economic benefits based on fewer f/u TLRs

16. MiStent Design Capitalizing on Lessons Learned and Novel Discovery
1. There is an undesirable consequence of both extremes, when the scaffolding is removed or inordinately thick— we have experienced this with both thick struts stents but also bioresorbable scaffolding
2. Elution of drug from the polymer is only a limited component of controlled drug delivery—formulation of drug, dispersion throughout tissue, duration of effect and dwell time are all essential and yet underappreciated components
3. MiStent incorporates advantages of stent-based and balloon-based systems, representing delivery of stent coating and drug yet independent of stent scaffolding
4. Crystalline formulation of sirolimus permits more uniform dosing, without focal excess or minimal concentrations, and without initial burst of drug release
5. Both by flow of coating and delivery of crystalline drug, there is a distinct advantage of drug persistence after polymer dissolution