Prof. Thomas ZellerDepartment AngiologyUniversity Heart-Center Freiburg - Bad KrozingenBad Krozingen , Germany

The MIMICS-2 IDE study: interim update on

BioMimics 3D in US, Japan, and Europe

Faculty Disclosure

For the 12 months preceding this presentation, I disclose the following types of financial relationships:

• Honoraria received from: Abbott Vascular, Bard Peripheral Vascular, Veryan, Biotronik, Boston Scientific Corp., Cook Medical, Cordis Corp., Gore & Associates, Medtronic, Spectranetics, Straub Medical, TriReme

• Consulted for: Abbott Vascular, Bard Peripheral Vascular, Boston Scientific Corp., Cook Medical, Gore & Associates, Medtronic, Spectranetics

• Research, clinical trial, or drug study funds received from:480 biomedical, Bard Peripheral Vascular, Veryan, Biotronik, Cook Medical, Cordis Corp., Gore & Associates, Abbott Vascular, Medtronic, Spectranetics, Terumo, TriReme, Volcano

Thomas Zeller, MD

Biomimicry: Platform for Stent Design Innovation

Vascular system uses

non-planar curvature to promote

swirling blood flow that protects

vessels by increasing wall shear

on endothelial cells and promotes

diffusion of Oxygen to the

arterial wall

Protective

Suboptimal

Pathogenic

1.5

0.5

7.0

Wall Shear Stress (Pascal)

1.

1. Malek et al JAMA 1999

What’s Unique about the BioMimics 3D stent?

SHORT co-linear connectors LONG co-linear connectors

LifeStentSPIRAL connectors

Unique BioMimics 3D design:SHORT + LONG connectors SPIRAL configuration

Zilver PTXComplete SE

… and 3D helical centreline in Nitinol shape memory.

Imparts non-planar curvatureto stented segment

Improves biomechanical performance 2

Promotes swirling flow to increasewall shear stress 1

1. Caro et al., 2013

2. Data held on file at Veryan Medical

MIMICS Clinical Program

Feasibility StudyN=101 site

MIMICS

RandomizedControlledvs. straight stent

N=508 sites24-month follow-up 1

CE Mark

MIMICS-2

Prospective, multinational evaluation of safety and primary patency at 12 months

N=27147 sites36-monthfollow-up

IDE Study (US, Japan, Germany)

MIMICS-3D

Prospective, observational evaluation within real-world clinical population

N=500+25 sites36-monthfollow-up

EuropeanPost-market Surveillance Registry

MIMICS et seq

Investigator-initiated and retrospective studies evaluating safety, efficacy and performance

Targets of interest:- popliteal- calcified lesions- DCB combination

Post-market & Geographic

1. Zeller et al Circulation CI 2016

Mimics Study: Lesion Characteristics

BioMimics 3D (N=50)

Control stent(N=26)

P value

Lesion Location SFA 92% 77% 0.08SFA/Popliteal 6% 12% 0.41

Popliteal 2% 12% 0.11TASC II A 42% 42% 1.00

B 56% 58% 1.00C 2% 0% 1.00

Lesion Length mm 66 ± 29 63 ± 28 0.66Stent Length mm 99 ± 30 88 ± 22 0.08Occlusion Total 44% 46% 1.00Calcification Moderate to Severe 52% 58% 0.81

Comparison with Other Studies

Superb Zilver PTX Durability II

Mimics IN.PACT LEVANT 2

Total Occlusions 25% 30% 48% 44% 25.8% 20.6%

Calcium (severe) 44% 37% 43% 42% 8% 17.6%

ControlBioMimics3D

2.25

2.00

1.75

1.50

1.25

1.00

0.75

0.50

Wall

Shear

Str

ess

(Pa)

In the Mimics randomized clinical trial, compared to Control stents, BioMimics 3D stents generated:

• 55% more swirling flow* (P= 0.017)

• 18% more wall shear stress (P= 0.054)

(n=42)(n=23)

* Swirling flow = Steady state adaptation of helical flow defined by Gallo J. Biomech. 45, (2012), 2398-2404

ControlBioMimics3D

0.00004

0.00003

0.00002

0.00001

0.00000

Sw

irlin

g F

low

(m

^4

s^

-2)

Swirling Flow & Wall Shear Stress

Data on file at Veryan Medical

Kaplan Meier Estimate of Survival from Loss of Patency

PSVR >2.0, or >50% diameter stenosis, or adjudicated, clinically-driven TLR

Mimics Study: Primary Patency

Log rank test

P = 0.05

80%72%

71%

55%

Months 246 12

0

20

40

60

80

100

__ BioMimics 3D

__ Control Stent

Cu

mu

lative

Su

rviv

al

24 Months12

0

20

40

60

80

100

Cu

mu

lative

Su

rviv

al

Log rank

test

P = 0.03

Kaplan Meier Estimate of Survival from CDTLR (Landmark Analysis)

(Clinically-driven TLR determined through Event Adjudication)

Mimics Study: Durable Benefit

__ BioMimics 3D

__ Control Stent

Mimics Study: Curvature Confirmed

Non-planar curvature in stented segment

Swirling flow patterns revealed by CFD modelling

Mimics Study: Real-World CurvatureIf lesion is heavily calcified, is curvature of the stented segment attenuated?

p = 0.14

% P

ate

ncy

Curv

atu

re m

m-1

240 6 12 months

20

40

60

80

100

0

Calcification

___none – mild

___moderate - severe

log rank test

p = 0.73

• Curvature and freedom from loss of primary patency are independent of calcification

Data on file at Veryan Medical

MIMICS-2 IDE StudyEvaluation of Safety and Effectiveness of BioMimics 3D in Femoropopliteal Intervention

• Primary Endpoints:

• Safety: composite of death, any major amputation performed on the index limb or

clinically-driven target lesion revascularisation (CDTLR) through 30 days

• Effectiveness: 12-month Primary Patency

• Follow-up: 3 years

• IDE Study extended to Japan through FDA/PMDA Harmonization by Doing Initiative

• 47 investigational sites: 35 US; 6 Germany; 6 Japan

Study Principal Investigators

Professor Timothy M. Sullivan, M.D Minneapolis, MN, USA

Professor Thomas Zeller, MD Bad Krozingen, Germany

Professor Masato Nakamura, MD Tokyo, Japan

• Independent core labs: ultrasound; angiography; clinical event adjudication

Enrolment Completed Oct-2016

N= 271 Subjects

Age Mean years ± SD (N) 68.4 ± 9.5 (271/271)Gender Male / Female 180 (66.4%) / 91 (33.6%)Risk Factors Diabetes Mellitus 45.4% (123/271)

Hypertension 90.0% (244/271)Hypercholesterolemia 81.9% (222/271)

Smoker Current / Former 80.8% (219/271)Cardiac History Coronary artery disease 46.1% (125/271)Previous Intervention None in target vessel 98.9% (268/271)Rutherford Category

1 0% (0/271)2 26.9% (73/271)3 67.5% (183/271)4 5.2% (14/271)5 0.4% (1/271)

Ankle Brachial Index Mean ± SD (N) 0.69 ± 0.20 (266/271)

MIMICS-2 IDE StudyBaseline Patient Demographics

MIMICS-2 IDE StudyBaseline Angiographic Characteristics

N= 271 Subjects

Reference Vessel Diameter2 Mean ± SD (mm) 5.18 ± 0.9Lesion Type1 De novo 100% (271/271)Lesion Location2 Prox SFA 9.0% (24/265)

Mid SFA 48.7% (129/265)Distal SFA 40.0% (106/265)

Prox Popliteal 2.3% (6/265)Lesion Length2 Mean ± SD (mm) 80.7 ± 38.2 (265/271)Occlusion2 Total 29.5% (80/271)Calcification2 None - Mild 53.6% (142/265)

Moderate - Severe 46.4% (123/265)Patent Infrapopliteal Vessels2 0 0% (0/252)

1 27.8% (70/252)2 52.0% (131/252)3 20.2% (51/252)

1. Per investigator

2. Core Lab

MIMICS-2 IDE StudyIndex Procedure Data

N= 271 Subjects

BioMimics 3D Stents placed1 # Stents / N 305 / 271# Subjects with 1 stent 87.5% (237/271)# Subjects with 2 stents 12.5% (34/271)# Subjects with 3 stents 0% (0/271)

Stented Segment Length2 Mean ± SD (mm) 112.5 ± 36.4 (265/271)Diameter Stenosis2 Pre-stent % ± SD 78.8 ± 22.1 (265/271)

Post-stent % ± SD 12.8 ± 8.0 (265/271)Dissections2 No Dissection 97.7% (259/265)

Type A-C 2.3% (6/265)Type D-F 0% (0/265)

Device Success 100% (271/271)Technical Success2 100% (265/265)

Device Success: Successful delivery of System; placement of stent and retrieval of System

Technical Success: Core Lab determination of ≤50% residual diameter stenosis (in-stent) at

conclusion of index procedure

1. Per investigator

2. Core Lab

MIMICS-3D RegistryProspective, multicentre observational study to evaluate BioMimics 3D in peripheral arterial disease

• Primary Endpoints:

• Safety: composite of death, any major amputation performed on the index limb or

clinically-driven target lesion revascularisation (CDTLR) through 30 days

• Effectiveness: 12-month Primary Patency

• Follow-up: 3 years

• Post-market surveillance study

• 25 investigational sites in Europe

Study Principal Investigator

Michael Lichtenberg MD Arnsberg, Germany

• Independent clinical event adjudication

Enrolment Ongoing

MIMICS Clinical Program

Feasibility StudyN=101 site

MIMICS

RandomizedControlledvs. straight stent

N=508 sites24-month follow-up1

CE Mark

MIMICS-2

Prospective, multinational evaluation of safety and primary patency at 12 months

N=27147 sites36-monthfollow-up

IDE Study (US, Japan, Germany)

MIMICS-3D

Prospective, observational evaluation within real-world clinical population

N=500+25 sites36-monthfollow-up

EuropeanPost-market Surveillance Registry

MIMICS et seq

Investigator-initiated and retrospective studies evaluating safety, efficacy and performance

Targets of interest:- popliteal- calcified lesions- DCB combination

Post-market & Geographic

1. Zeller et al Circulation CI 2016

Prof. Thomas ZellerDepartment AngiologyUniversity Heart-Center Freiburg - Bad KrozingenBad Krozingen , Germany

The MIMICS-2 IDE study: interim update on

BioMimics 3D in US, Japan, and Europe