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When nature fails, technology takes over: Innovative

Solutions by Flux Medical

Anne-Rose Gustin Chief Operation Officer

Flux Medical

annerose.gustin@pandora.be

When nature fails, technology takes over:

Innovative Solutions by Flux Medical

in cooperation with Verhaert

3.3 3.4 3.5 3.5 3.6 3.6 3.73.4

3.4 3.5 3.6 3.9 4.2 4.62.9

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2.4 2.3 2.42.7

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2.1

1.2 1.41.6

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Glenn Van Langenhove, Chief Executive Officer and founder

MD, PhD, MBA

Interventional cardiologist, Middelheim Hospital

Medical Director Thermocore (2000-2009), technology successfully

licensed to Bristol Myers Squibb

President Belgian society of Interventional Cardiology

Expert in stenting business

Bruno Schwagten, Chief Scientific Officer and founder

MD, PhD

Cardiologist - Electrophysiologist, Middelheim Hospital

Entrepreneur in residence,

EP training Erasmus University, Rotterdam, The Netherlands

Co-founder of the Society of Cardiac Robotic Navigation

Expert in cardiac arrhythmias

Anne-Rose Gustin, Chief operations Officer

Manager of Safety & Prevention, Quality and Environment, Carestel

NV and Thermocore Medical Systems,

Managing partner Incubate Cardiac Solutions

Master degree in Eastern Languages/Sinology/Japanology

Special degree in Business Communication

Team

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Atrial fibrillation

Caused by abnormal electrical impulses originating in the pulmonary veins

Symptoms: palpitations, fainting, chest pain, decreased quality of life

Outcome: severe stroke and congestive heart failure leading to death

1 in 4 above 40 and increasing - currently 2.5 million patients treated in US

alone

High cost to society: 6.5 billion USD in US annually (Source: CDC)

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Atrial fibrillation

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Single invasive treatment

not requiring follow-up

medication

Successrate: 50 – 60%

10,000 EUR per procedure

(reimbursement in place in

Europe and US)

Complex:

- requires highly skilled

team

- dedicated electrophys lab

Recognised first line

treatment in new guidelines

in Europe and US

Chronic treatment with

medication

Successrate: 30-40%,

with frequent side effects

4,000 EUR per year per

person medication cost

1 in 3 patients do not

tolerate medication

Medication can induce

life threatening

arrhythmias

Ablation Medication

* ESC = European Society of Cardiology

ACC= American College of Cardiology

AHA= American Heart Association

AF treatments as per current ESC, ACC, AHA Guidelines

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Aberrant signals are blocked by creating a line of scar tissue between

the pulmonary source of the signal and the muscles of the left atrium

• Difficult lenghty procedures special team required 10,000 EUR per patient

• Possible perforation of the vessel wall , damage to surrounding tissues / nerves, collateral

damage to the left atrium due to imprecise ablation

• Reconnection leads to invasive redo and is required in 50% of cases within 2-5 years

• Radiation exposure to patient and operator

Point by point treatment Single shot devices

Disadvantages adressed by the Flux system

Treatment principle

Treatment options

Current ablation treatments

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Procedure

• One stent-like device per pulmonary vein

• A circular heating coil in the stent touches the full circumference of the vein

• Externally applied magnetic energy heats the coil until the electrical

currents from vein to atrium are fully interrupted

• The stent includes a full set of safety features

Competitive edge over currently used ablation procedures

• A simple, low-risk, standard procedure compared to current ablation

treatments

• Reduced procedure time: increasing capacity of the cathlab

• Reduced collateral damage to surrounding tissues and atrium

• Reduced radiation damage to the operator and patient

• Repeat procedures are possible, non-invasive, quick and simple

• This procedure does not compromise future surgical intervention if needed

• Significant cost advantage to society

• High profit margins on the device and procedures

Medical device developed by Flux

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IP protection

Search for investors

R&D:

• Engineering subcontractors

• Scientific path from modelling to first in man

• From concept to proof of concept

From Concept to Realisation:

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Verhaert NV - Belgium Experience:

Leading engineering company with a track record in design of

satellite components, medical devices (orthopaedic), products

combining electronics with advanced material sciences Provide to Flux:

Stent engineering - Magnet design development - CE certification

Feops NV - Belgium Experience

Biophysics, modelling of physiological processes, prototyping

of virtual medical devices Provide to Flux:

Prediction of the physical parameters and behaviour of the human pulmonary

veins

Anatomic and physhiological feasability analysis & definition of stent parameters

Contract Medical International (CMI) – Dresden Germany Experience

Leading stent manufacturer Provide to Flux:

Development and manufacturing of stent prototypes for animal

and human trials. Candidate for future stent production

Engineering Subcontractors

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Research phase Development phase Human trials

Animal model Animal trials First In Man

In vitro/in vivo In vivo In vivo

University of Ghent Merelbeke

Paris Singapore

Affiliated Electrophysiology Centers across Europe and VS

Efficient, nearby, low cost High quality, complete file Reliable and fast

Scientific path from modelling to first in man

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Question Workpackage Subcontractor Outcome

Anatomical variability of pulmonary veins

• Literature • FEA: CT scan of 100 pts • PyFormex • Slicer 3D

• >90% pts eligible for implant • custom made implants • presented at Cardiostim 2012 • submitted JACC

From concept to ex vivo proof of concept

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Question Workpackage Subcontractor Outcome

Stretchability of pulmonary veins

• Ex-vivo animal trial •Prelevated specimens of weight matched sow hearts

• safe stretching x1.8 times • huge safety margin for implants

+ 120% + 80%

From concept to ex vivo proof of concept

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Question Workpackage Subcontractor Outcome

Radial forces

required for vein

scaffolding and

implant fixation

• FEA: software

model used for

coronary artery

stenting, including

variables of vein

thickness and size,

strut size, implant

diameter and length

• feasible for self-

expanding device

• definition of device

design parameters

From concept to ex vivo proof of concept

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Question Workpackage Subcontractor Outcome

Selection of optimal

energy used by

implant

• Engineering study

on energy sources

• Iterative material

bench testing

• Multiple in vitro

trials

• Induction heating

by magnetic field

• Selecting optimal

alloy

• Magnet properties

and design

• Coil properties and

design

From concept to ex vivo proof of concept

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Question Workpackage Subcontractor Outcome

Device prototyping

• Breadboarding

• Bench testing

• In vitro and ex vivo

testing

• Prototype ready for

in vivo animal trials

From concept to ex vivo proof of concept

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Question Workpackage Subcontractor Outcome

Controlled heating

of the implant

• Breadboarding of

control mechanisms

• Bench testing

• Incorporation in the

implants

• In vitro and ex vivo

testing

• Controlled heating

within range of 1

degree Celcius is

feasible

• Homogenous

lesion formation in

ablated tissue

From concept to ex vivo proof of concept

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•Long procedure •Chance of repeat procedures due to incomplete conduction block •Surgeon exposure to X-Rays for visualisation of catheter position

Current state-of-the-art

•Single incision for placing implant •Entire circumference of vein is treated at once reducing procedure time •Multiple veins can be treated simultaneously reducing procedure time •Repeat procedures are possible, quick and simple •Ablation procedure can be performed without the direct attention of a surgeon

Proposal

Goals: •Technology investigation •Initial feasibility of technology •Application ideation Actions: •Desk research •Brainstorm sessions •Initial patent screening •Initial modelling •Criteria exploration (regular interaction with Flux Team) Results: •Morphological chart of solution options •First trade-off •Hysteresis heating shows potential for safe, controlled heating – Further testing required •Joule heating and eddy current heating as alternative options

Phase 1 - Feasibility

Goals: •Practical verification of hysteresis heating •Material selection •Parameter investigation Actions: •Breadboard testing of various materials (Fe3O4 and ZnFe2O4, 2x Ferrofluids) •Testing parameter influences (Frequency, field strength, material mass) •Initial thermal modelling •Initial magnetic modelling Effect of insulation (thermal & electrical) Results: •First characterisation of frequency, field strength and mass effects •Steady Sate and Transient Thermal model •Magnetic model •Hysteresis heating achieved (Fe3O4 and Ferrofluid show potential, but efficiencies are too low • Refocus on Joule heating with temperature sensing Phase 2 –

Technology breadboarding

Goals: (Current Phase) •Ablation of tissue •Temperature control •Initial implant design •Initial applicator design •Formal risk assessment Actions: •Breadboard testing of various implant designs and temperature sensing technologies (Bi-Metal switch, PTC, Polyswitch, Digital Thermostat...) Results: •Heating efficiency of Joule heating is much higher •Ablation of tissue samples (pig heart vessels) achieved •Temperature control achieved in lab environment • Implant design iterated • Applicator concepts created • Risk File

Phase 3 – System Breadboarding

Goals: • Use all data and information to build a demonstrator • “Looks like real” – A dimensionally correct model to get the look and feel of the final product • “Works like real” – A fully functional system model for performing tests Actions: • Detailed system design of equipment and implant • Assembly of demonstrator • Test campaign with demonstrator • Quality assurance options

Phase 4 – Demonstrator

Go

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Goals: • Use all data and information to build a prototype • Prototype to perform ablations during clinical trials •Application ideation Actions: • Detailed design of equipment and implant • Manufacture and assembly of prototype • Clinical trials with prototype • Quality assurance

Phase 5 – Detailed Design, Prototype & Clinical Trials

Go

/no

-go

Goals: • Final design for production • Production of first series • Batch production Actions: •Detailed design of equipment and implant taking into account manufacturing methods, materials and costs • Manufacture and assembly of product • Quality assurance

Phase 6 – Production

Go

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-go

Proposal

Achieved

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Material on Implant

•How do we get the active material in/on the implant

Reduce Blood Cooling Effect

•Difficult to control factor is blood cooling of the implant and active zone, how can this be reduced

Other Foldable or Flexible Mechanisms

•Are there other ways to place the material apart from or connected to a stent

Out There

•Parking area for miscellaneous and far out of the box ideas

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IN0111 – Magnetic Ablation

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Thermal Analysis

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