SUPRAFLEX - Next generation ultra thin sirolumus eluting stent produced by SMT proudly supported in Italy by EUKON

1. 1
The latest Generation of Sirolimus-Eluting Stent

2. 2
Contents
1. Supraflex Summary
2. Key Features: What makes Supraflex unique
• Lowest Thickness
• Flexible Open Cell Design
• Broadest Size Matrix
• Biodegradable Polymer Coating
• 15 years of DES manufacturing experience
3. Clinical Trials and Publications

3. 3
Supraflex: Summary
Infinnium
from SMT
Bio matrix
2005 2008 2010
Bio matrix
Flex
2011
Supralimus
Supralimus- Core
Yukon-Choice
Orsiro
2013
Synergy
from Boston
Scientific
CE Approval Timeline

4. 4
Contents
1. Supraflex Summary
2. Key Features: What makes Supraflex unique
• Lowest Thickness
• Flexible Open Cell Design
• Broadest Size Matrix
• Biodegradable Polymer Coating
• 15 years of DES manufacturing experience
3. Clinical Trials and Publications

5. 5
Platform: Lowest Strut Thickness in
market while similar radial strength
Lower strut thickness is associated with lower restenosis rates1
1Allison C Morton et al, Pathologies Biologie 52 (2004) 196–205 “The influence of physical stent parameters upon restenosis”
Cypher Taxus
Express
Taxus
Liberte
Endevor
Resoulte
Integrity
Xience V
Xience
Prime
Yukon
Choice PC
Promus
Element
Supralimus® Supraflex™
Coating Thickness
12.6 µm 19.6 µm 14.0 µm 6.0 µm 8.0 µm 8.0 µm 4-5 µm 5-6 µm
850 mm Hg 810 mm Hg
Comparable radial strength
25% less Strut Thickness
L605 Co Cr Alloy
Avg Ni<9,5%

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Metal/Artery Ratio and Crossing Profile
• Lower M/A ratio minimizes risk of vessel wall injury and other long term adverse outcomes1
• Minimum Crossing Profile allows easier passage through tighter lesions and use of smaller
guide catheters
Supraflex Promus
Element
Xience
Prime
Resolute
Integrity
9.02
14.5 13.3
18.1
Metal to Artery Ratio (%)
Supraflex Promus
Element
Xience
Prime
Resolute
Integrity
1.1
1.17
1.24
1.17
Crimping Profile (mm)
1. Merie-Claude Morice, The Journal of Invasive Cardiology, Vol 15, Issue 9, 2003, ”Stenting for Small Coronary Vessels “

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Foreshortening and Recoil
Foreshortening (%)
• Minimal foreshortening ensures accurate deployment and precise lesion coverage2
• Minimum stent recoil helps reduce risk of strut malapposition and improves immediate and
log term procedure outcome3
Recoil(%)
Supraflex Promus
Element
Xience Prime
1.13
7.5
1.8
Supraflex Promus
Element
Xience
Prime
Resolute
Integrity
2.92 3
4.7 4.9
2 John F LaDisa et al, BioMedical Engineering OnLine, 2005, 4:59, “Axial stent strut angle influences wall shear stress after stent implantation: analysis using 3D computational
fluid dynamics models of stent foreshortening”
3 Barragan et al, Catheter Cardiovasc Interv. 2000 May;50(1):112-9,” Elastic recoil of coronary stents: a comparative analysis

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Excellent Deliverability
• Lower Trackforce implies that Supraflex has excellent deliverability in challenging lesions
• Supraflex has been laboratory tested for challenging lesions to confirm its excellent
deliverability
Supraflex Brand A Brand B
0.768
0.938
1.09
Track Force(N) Vessel Model used for Track Test
≈37cm
Curve 4 ≈75cm
Curve 3≈69cm
Curve 2≈63cm
Aortic Arch Curve 1≈47cm
≈85cm

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Supraflex: Size Matrix & Compliance Chart
08 12 16 20 24 28 32 36 40 44 48
2 √ √ √ √ √ √ √ √ √ √ √
2.25 √ √ √ √ √ √ √ √ √ √ √
2.5 √ √ √ √ √ √ √ √ √ √ √
2.75 √ √ √ √ √ √ √ √ √ √ √
3.0 √ √ √ √ √ √ √ √ √ √ √
3.5 √ √ √ √ √ √ √ √ √ √ √
4.0 √ √ √ √ √ √ √ √ √ √ √
4.5 √ √ √ √ √ √ √ √ √ √ √
Length (mm)
Diameter(mm)
Nominal Pressure
Rated Burst Pressure
1 ATM = 1.01 bar

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Biodegradable coating on Supraflex
• Conformal coating with thickness of ~ 5 µm over stent strut
• Optimized drug dose of 1.4 µg/mm2 with biphasic drug elution up to 48 days
• Lower drug-polymer load on stent
• Decreased risk of late adverse events due to utilization of biodegradable polymers (PLLA,
PLGA and PVP)

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• Biodegradable polymers are selected based on their hydrophobicity,
hydrophilicity and crystallinity
• SMT has optimally chosen following polymers for its DES
– Poly L-Lactide (PLLA)
– Co-polymer of L-Lactide and DL-Gycolide (PLGA)
– Polyvinyl pyrrolidone (PVP)
• Finding optimum balance between PLLA, PLGA and PVP, allows proper
control of drug elution and coating integrity
• Layer by layer coating arrangement allows multiphase release profile
O
O
O
O
n
O CH
CH3
O CH
CH3
C O CH2C O CH2C C
n
O O O O
CH2
CH2
C=O
N
CH
CH2
CH2 n
PLLA
Semi-crystalline hyrophobic polymer
PLGA
Amorphous and hyrophobic polymer
PVP
A hydrophilic
polymer
SMT Biodegradable Polymers

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Supraflex: Drug Release and Restenosis
Cascade
Drug release is designed to occur in two phases
1. Initial burst
Post stent implantation, smooth muscle cell
(SMC) proliferation initiates which is one of
the major contributing factor of restenosis.
The initial high level of drug release will take
care to prevent excess cell growth
2. Sustained release up to 7 weeks
To maintain the sufficient amount of drug
level in the arterial tissues, SMT stents are
designed to deliver drug at sustained rate up
to about 7 weeks after implantation. Representative in-vitro drug release
0
20
40
60
80
100
0 7 14 21 28 35 42 49
Cumulativedrugrelease(%)
Time (days)

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Supraflex: Coating Integrity
1 ASTM F2743 – 11: Standard Guide for Coating Inspection and Acute Particulate Characterization of Coated Drug-
Eluting Vascular Stent Systems
• Intact coating surface (without any
irregularities or scratches) observed
in crimped state
• Homogeneous and smooth coating
surface of expanded stent without
any deformation or cracking
• Particulate matter shedding
evaluation showed excellent coating
characteristics and passed the
acceptance criteria.1

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Contents
1. Supraflex Summary
2. Key Features: What makes Supraflex unique
• Lowest Thickness
• Flexible Open Cell Design
• Broadest Size Matrix
• Biodegradable Polymer Coating
• 15 years of DES manufacturing experience
3. Clinical Trials and Publications

15. 15
Clinical Excellence and Publications
Department Abstracts/
Publications
Journals
R&D 12 Trends in Biomaterials and Artificial Organs, Journal of Biomaterial
Application, etc.
Pre-Clinical 4 IJC, Journal of Biomaterial Application, etc.
Clinical > 40 Euro intervention, JACC, etc.
Indolimus is the additional brand of Supralimus-Core
More than 12,000 Patients

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Flex Registry
Favourable Healing Index
Supraflex = 4.8
Xience = 10.8
Resolute = 18.7
BioMatrix = 35.3

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Flex Registry OCT
Favourable Healing Index
Supraflex = 4.8
Xience = 10.8
Resolute = 18.7
BioMatrix = 35.3
1) Presence of intraluminal defect (intraluminal defect area both free from the wall
and attached to the lumen/stent area) (weighting factor of 4)
2) Presence of both malapposed and uncovered struts (weighting factor of 3)
3) Presence of uncovered struts alone is (weighting factor of 2)
4) Presence of malapposition alone (weighting factor of 1)
5) Neointimal volume obstruction of >30% (weighting factor of 1)

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S Flex UK registry
Interim analysis: 208 patients (12 months follow-up)
Events n=208 Patients
Death, n (%) 4 (1.9%)
Cardiac death, n (%) 2 (1.0%)
Non-cardiac death, n (%) 2 (1.0%)
Myocardial infarction, n (%)
3 (1.4%)
Target lesion revascularization, n
(%)
6 (2.9%)
Non target lesion TVR, n (%)
4 (1.9%)
Stent thrombosis, n (%) 0 (0%)
Target lesion failure (Cardiac
death, Target vessel MI & TLR) at
12 months, n (%)
8 (3.8%)
Total no. of enrolled patients
n=478 (July-2015 to November-
2016)
No. of patients that completed a
12 months follow-up (n=217)*
No. of patients included for
interim analysis (n=208)
Excluded patients (n=9)
Reason for exclusion:
1. Removed patients,
n=2
2. Stopped data entry,
n=2
3. Refused patients, n=3
4. Scheduled end of
study with no reason,
n=2

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TALENT Trial

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TALENT Trial
Enrollment finished in July 2017

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TALENT Trial

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TALENT Trial
All-comers PCI population
(ACS and Stable CAD patients)
Supraflex SES Xience stent EES
.
1 Month (+7 days) - Clinic Visit + ECG
6 Month (+14 days) - Phone contact
Randomization 1:1
(N = 1,430)
12 Month* (+30 days) - Clinic Visit + ECG
3 Year* (+30 days) - Phone contact
2 Year* (+30 days) - Phone contact
Both stents are CE marked
*All one-year follow-up visits must be scheduled at least at one year after randomization (and henceforth not earlier).
This also applies to the scheduling of the 2 and 3 year visits.

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Supraflex: Clinical Trials Program
Multi-centre, Single-arm, All-comers, Observational Registry
N=995 Patients, (Completed)
Retrospective, Single-arm, Non-randomized, Multi-centre Registry
N= 995 Patients (231 DM vs. 764 Non DM ), (Completed)
FLEX Registry
Diabetic Subset
Supraflex-Optical Coherence Tomography Evaluation
N=77 Patients, (Completed)
Supraflex OCT
Subset
Retrospective, Non-randomized, Observational, Multi-centre Registry
N= 240 Patients, (Completed)
Long lesion Subset
Retrospective, Single-arm, Non-randomized, Multi-centre, Post marketing
Surveillance Study N= 185 Patients (43 DM CTO vs. 142 Non DM CTO),
(Completed)
CTO in Diabetic vs.
Non-Diabetic Subset
Single Centre, Retrospective Study
N=59 Patients (Supraflex=30 and Xience Prime=29), (Completed)
Conformability
Study
Sflex UK Registry
Prospective, Observational, Multi-centre, Post Marketing Registry
N= Approx. 500 Patients, (Ongoing)

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Supraflex: Clinical Trials Program contd.
Multi-Vessel Subset Retrospective, Multi-centre, All-comers, Observational Study
N= 995 Patients (769 Single vs. 226 Multi-vessel(Completed)
Large Vessel
Subset
Retrospective, Single-arm, Open-label, Multi-centre Registry
N= 46 Patients, (Completed)
Small Vessel
Subset
Retrospective, Single-arm, Open-label, Multi-centre Registry
N= 995 Patients (351 Small diameter vs. 644 Non small diameter), (Completed)

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Supra Family - Clinical Trials Program
First-in-man, Single Centre, Prospective Study
N=105, Completed
Single group Pharmacokinetic study
N=20, Completed
Safety and Efficacy Trials:
MAXIMUS FIM
PK Study
First-in-man, Single Centre, Prospective Study
N=12, Completed
OCT Study
Prospective, Single-center and Non-randomized study
N=19, Completed
Recoil Study
Non-randomized, prospective, multicenter registry
N=335, 3-yrs Follow-Up Completed
PMS Registries:
SAUDI Registry
Observational, single-arm, non-randomized registry
N=562, 1-yr Follow-Up Completed
S-CORE Registry
Multi-center, retrospective, observational study
N=60, Completed
Dual Vessel PCI
Subset

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SMT Continuous Innovation
Supraflex
“Cruz”
SMT’s 4th
Generation DES

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Proudly supported in Italy by: