Measuringbrainvascularstatusatthetimeofprecisionmedicine

CompanyPresentation

Feb2018

WeareLuciole Medical…

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Wearescientists,engineersanddoctors

ETHistheleadingscienceinstitutewhereAlbertEinsteinstudied

Oneplatform,twoproducts

Weprovidephysicianswithinformationtoact

Theplatformhasoneproduct(minimallyinvasiveprobe)withCEmarkinEuropeandanticipatetoobtaintheCEmarkforthesecondproduct(patch)inthecomingyear.

Aswellrecognizedtheacuteinsufficientoxygenavailabilityinthebraincanhavesevereconsequences.Thechronicalortemporaryreduced/sub-acuteoxygenationisoftenundetectedandhasseriousconsequencesonthebrainsuchascognitionimpairment.

Wewantourtechnologyandproductstohelpdoctorsandsavepatients!!and…weareonamission!

Luciole MedicalisaSwissmedicaltechnologycompanydevelopingbrainoxygenationmonitoringsystems.WearelocatedinZürich.

Thecompanyhasdevelopedauniqueproprietarytechnologymakingthemeasurementofthetrueoxygencontentandbloodflowofthebraintissuepossible.

Whyisitimportanttomeasuretheoxygenationofthebrain?

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Thehumanbrainrepresents2%ofthebodyweight…consumes15%to20%oftheoxygenofthebody

3%ofthepopulationhaveananeurismintheirbrain

25%ofpatientsundergoingcardiacsurgeryhavepostop.cognitivedysfunction

Itisproventhatimpairmentofcirculation(andthusoxygenation)playsaroleindegenerativedisease:CVDisCerebralVascularDementia

Thebrainisacomplexandhighlyregulatedorgan,oneparameterisnotsufficienttocapturethewholepictureofwhatisgoingonandtoinitiatethebesttreatment

PrecisionMedicineandA.I.

Importantmedicalneed andcommercialopportunity

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Traumaticandacutecompromisedoxygensupply

§ TraumaticBrainInjury: 1.7mio intheUSperyear,55’000deaths,USD60bn incosts

§ Brainbleeding(aneurism) 9to20per100’000people§ SecondaryVasospasm

Hospitalconditions:surgery

§ RoleofthelowbloodperfusioninthedevelopmentofVasculardementia

§ Monitoringofvariousdegenerativebrainconditions§ Newparameters:watercontentandICP

Emergingopportunities

§ Deaths,coma§ Neurological:paralysis, speaking

impairment§ Cognitiveissues

§ Cardiacanesthesia§ Anesthesiamonitoring

§ 25%ofcardiacsurgerypatientshaveseriouspostoperativecognitiveissues

LuciolePatch

LucioleProbe

Increaseddemandfrommedicalcommunity

Auniqueversatilemultimodalmonitoringsystem

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RheoSens RheoPatch RheoControl UnitandMonitor

§ Implantable singleuseprobe

§ IntensiveCareUnit

§ Forpatientincomaafterhaemorrhageorseveretrauma

§ Oneprobereplacinguptothreeconventionalprobes

§ Adhesivepatchappliedtotheskinontheskull

§ Deliversbrainbloodflow,brainbloodvolumeandoxygen

§ Forpatientduringsurgeryorconscious.

§ Canbeusedtogetherwithprobe

§ PocketsizedNIRS1) controlunitemitter

§ RheoControl Unitallowsformodularexpansionupto6devicesperpatient

§ USBPluggedinmedicalmonitors

1) NearInfraredSpectroscopy

1)Near-InfraRedSpectroscopy

Theplatformistheonlyoneabletomeasurethecontentinoxygenatedanddeoxygenatedhaemoglobinallowingthedoctorsto:

- Rapidlyidentifytheischemia- Understandtheorigin(flow,anaemia,..)- Design,implementandfollowthebesttreatment

OurUSP

Twolargegrowingmarketsegmentsrepresentamultibillionopportunity

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Millioncriticalcarepatientsannually

Milliongeneralanaesthesia

patientsannually

Millioncardio-anaesthesia

patientsannually

Anaesthesia AdditionalapplicationsCriticalcare

§ ValidationmarketforRheoSens andRheoPatch:§ Subarachnoidhaemorrhage§ Traumaticbraininjury§ Severestroke

§ Criticalcaremarketrepresents3millionpatientsannually

§ Currently,2millionofcriticalcarepatientsqualifyforRheoPatch and0.5millionforRheoSens

§ InitialfocusmarketforRheoPatch isthecardiacanaesthesiamarket,representing4millionpatientsannually:§ Cardiopulmonarybypasssurgery§ Othercardiacsurgery

§ Generalanaesthesiainhighriskandelderlypatientswillfollow,representing14millionpatientsannually

§ Currently,1millionofallcardiacanaesthesia patientsqualifyformonitoringwithRheoPatch

§ RheoPatch:§ Sleepapnea

(30mpatientsintheEU,US,Japan)§ Transientischemicattack

(1meligiblepatientsannually)§ Traditionalpulseoximetrymarket

(over$2bnmarket)§ Telemedicine/e-health§ Predictionsoftware§ Asthma/chronicobstructive

pulmonarydisease§ Post-cardiacarrestcare

§ RheoSens:§ Osteosynthesis§ Muscularcompartmentsyndrome§ Reconstructivesurgery§ Oralsurgery§ Organtransplantation

JapanUSEurope

1.9

6.61.5

5.3

2.1

Generalanastheasia

14.0

Cardio-anastheasia

4.00.6

Europe JapanUS

1.6

1.0

0.4

3.0

Criticalcare

1)#ofpatientsperyearinmillions

1)

1) 1)

Basisforsuccess

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Firstclassuniqueproductwithclearpathtomarket

Largegrowingmarketwithundisputedmedicalneed

Largelyde-risked

Attractivevaluationandlowcashburn

Luciole MedicalsolvedscientificproblemsinNIRS andmadethetechnologyfitforuse

clinically,regulatorypathway,industryconfirmation,partiallycommercially

- Twodifferentiatedmarketsegments- Potentialforcompetitivepricingandlowreimbursementhurdle

Turnaroundopportunitywithnoliability:executionplay

Keydatapointstogenerateconcreteshorttermvaluecreationandexitopportunities

Shorttermvaluegeneration

Attractiveaccelerationopportunity

Luciole MedicalhasanexperiencedleadershipteamwithstrongexecutionskillsNewtalentswilljoinuponfinancing

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Luciole Medicalisanawardwinningcompany

Luciole MedicalhasreceivedtheCertificateforaQualityManagementSysteminOct2014

Strongscientificposition:- 18peerreviewed

publicationsinrenownedjournals

§ Prof. Emanuela Keller,MD,FounderHeadoftheNeurocritical CareUnit,Dep.ofNeurosurgery,UniversityofZϋrich

§ Prof. JavierFandino,MDDivisionofNeurosurgery,Kantonsspital Aarau

Advisors

§ Prof.DanielA.Rüfenacht,MDProf.ofNeuroradiology,KlinikHirslanden,Zϋrich

§ Prof.JoseI.Suarez,MDBaylorCollegeofMedicine,NeurosensoryCentreofHouston

§ PhilippeDro,PhD,MBACEO&ChairmanoftheBoard§ FormerCEOofGlycoVaxyn§ FormerCEOofEndoArt§ Co-FounderofAxovan

§ MarkusH.Muser,PhDMemberoftheBoard§ Over25yearsexperienceinengineeringandmedicine,

medicine,inventorofseveralpatents§ Co-founderandco-ownerofAGUZϋrich

§ BrunoReihl,PhDMemberoftheBoard§ FormerCTOanddeputyCEOatDisetronic§ FormerCEOofRaumedic§ Founderofseveralcompanies

§ JürgFröhlich,PhD,CSOElectromagneticsinbiomedicalapplicationsandBiomedicalPhotonics§ FormerAssociateDirector,IT’ISFoundation,Zurich§ FormerGroupleaderElectromagneticsinMedicineandBiology,ETH§ VisitingSeniorResearchFellowNUS,Singapore§ Co-FounderofFieldsatWorkGmbH,Zurich(Spin-OffETHZurich)§ Co-FounderofPiomic MedicalAG,Zurich

• DirkBaumann,PhD,HeadDevelopmentmanagesthedevelopmentofsoftware,algorithmsandhardware§ InternshipattheUniversityofFairbanks,Alaska§ ResearchAssistant/Phd StudentETHZurich§ FormerResearchEngineeratA*STAR,Singapore§ PostDoc BiomedicalPhotonicsETHZurich

§ MedIdee SAMedidee isaQA/regulatoryboutiquewithexpertisebothinEUandUSThecompanyisactivelyinvolvedwithsupportingLuciole Medical.AQAmanagerwillbehireduponclosingofSeriesA

Board KeyTeamMembers

Investmentcase:Cuttingedgetechnologyatprecommercialstagewithlargeupsidepotential

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Technology&Products Uniquenewgenerationplatformprovidingvascularandmetabolicinformationfordiagnostic,treatmentandmonitoring

Medical Need&Market Verylargeunmetmedicalneed:monitoringofcerebraloxygenationinvariousmedicalconditions:- ICUmarket:USD500millionperyear- Anesthesia:USD1+bn- Emergingnewindicationsandmarkets

Stage ofDevelopment With humandata,CEmarkandearlymanufacturingcapabilities,thecompanyislargelyde-risked.Buildingofrelationshipwithindustryalreadystarted,interestconfirmed.Ready forcommercialization(EU)andregulatoryactivityinlargeterritory(US)

FinancingneedandTerms Financingroundinpreparationforearly2018TargetisatotalofCHF 5to8 millionInvestedsofar:CHF10million(7 inequity/3grants)

Clear valuecreationpath Shapethecompany assolidinnovativeplaybecominganattractiveacquisitiontarget:- SaleandPipeline- 2010AcquisitionofSomanetics byCovidienforUSD250mio

AdditionalInformation:

ClinicalCase*ManagementofaPatientinHypoxiaconsecutivetoaSubarachnoidHemorrhageduetoAneurysmRupture

*CasewashandledinZürichUniversityHospital,dept.ofNeuroIntensiveCarebyPr.E.Keller,founder

Clinicalcase:subarachnoidhemorrhage

1. Lowoxygensupply(O2 ↓)

2. Lowoxygencarrier(hemoglobin;anemia)

3. Lowbloodflow(CBF)

4. Highoxygendemandofbraincells

• Only 1/3of patients survive with mildor nodisabilities

• 1/3of patients develop cerebral vasospasmleading to ischemia &secondary infarctions

• Deathor severe disability inallpatientswith vasospam refractory to treatment

Vasospasmè ischemiaè infarctions dueto:

IschemiainIntensiveCareUnit:Whatdoesitmean?

Day0:ruptured aneurysm:bleeding inthe brain

brain vessels constrictedè imminentischemia

Consequences:Afterseveraldaysthepatientisdevelopingvasospasmsthatcanleadtoseveredamages.

Thisischemiacan’tbedetectedasthepatientisin

coma.

Clinicalcase:treatmentcascadeofSAHwithvasospam

1. Correctanemia è increase of oxygen carrier (hemoglobine)concentration

2. Treatfever è decrease oxygen demand

3. Artificialhypertensionè increase blood flow

4. Balloondilatationoflargecerebralvesselsè increase blood flow

5. Intraarterialvasodilatorsè increase blood flow

6. Therapeutichypothermiaè decrease metabolism(“hibernating”)

Ø Precisionmedicine:TheORIGINof ischemia is to be identified to decide

which treatment(s)is specifically adapted to the each patient

Paradigmshift:precisionandpersonalizedmedicine

https://www.whitehouse.gov/precision-medicine

Clearneedforneuromonitoring

O2–delivery O2–consumption

given by:• O2 content (~Hboxy)• hemoglobin (carrier of O2)• blood flow (CBF)

ischemia = dysbalance

Luciole Systemmeasures• CBF• Hboxy

Luciole Systemmeasures• Hbdeoxy

given by:• cell metabolism• O2 need (~Hbdeoxy)

Luciole Systemmeasures• SbtO2

Sbto2:agoodindicatorofhypoxia

ischemia with ptiO2 <15-20mmHg

Reasonforischemia?

1. Lowhemoglobin?

2. LowO2 content/delivery?

3. LowCBF?

4. HighO2 need?

Thesystemcandetectischemiaearlierthanothermeasures

SbtO2is the earlier indicator for ischemia(>1min.)than ptiO2

è Starttreatment earlier with Luciole System

CerebralBloodFlowmeasuresgivesoriginofischemia

CBF↓

ContinuousmeasureofHboxy,Hbdeoxy indicatescauseofischemia

Hbdeoxy↑è O2 need↑

Hboxy↓è O2 delivery ↓dueto CBF↓

SbtO2=Hboxy/Hbtotal

dueto blood pressure drop↓

Initiateandmonitorthebesttherapeuticaction(s)

Hbdeoxy↑è O2 need↑

Hboxy↓è O2 delivery ↓dueto CBF↓

SbtO2=Hboxy/Hbtotal

dueto blood pressure↓

è Treatment:1.Increase blood pressure to increase bloodflow &O2 delivery (monitor impact onCBF&Hboxy)

è Treatment:2.induce hypothermia to decrease O2need(monitor impact onCBF&Hbdeoxy)

Induction of hypothermia

Hbdeoxy↓è O2 need↓

Controleffectivenessoftreatment:reductionofmetabolism

Induction of hypothermiaArtificial increase of blood pressure

Hboxy↑è O2 delivery↑

Controleffectivenessoftreatment:increaseofO2delivery

Conclusions

• Oximetryvalues obtained with the Luciole Systemare valuable

• SbtO2 values behave similarly to ptiO2 values

• Hboxy andHbdeoxy values are inclose relationship with clinical events

• Luciole Systemallows detection of brain ischemia earlier

(SbtO2 reacts earlier than ptiO2)

• Multiparametermonitoring with the Luciole System,

delivering CBF,SbtO2,Hboxy andHbdeoxy allows

• to identify the exact cause of ischemia

• to enable causal treatment of ischemia

• to control the effectiveness of treatment

• to explore new neuroprotectivetherapies

Thankyou!

Luciole: pronounced:lysjɔl (“Lüssiol”)FrenchwordforFirefly(Eng.);Glühwurm (Ger.),Lucciola (Ita.)

FlyinginsectofthefamilyofLampyridae havingtheproperty toemitfluorescentlightbetween510and640nmwavelengthandshowingamovinggreendotinthenight.

Similartothetechnologyusedbythecompany(NIRS)tomeasureoxygensaturationofbraintissue.

Contact:PhilippeDro,CEOemail:philippe.dro@luciolemedical.chwww.luciolemedical.ch

Luciole MedicalisthesuccessorcompanyofNemoDevices AG