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SilverSkyInsights:ECCMID2018Impressions

SilverSkyInsights:ECCMID2018Impressions

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SilverSkyInsights:ECCMID2018ImpressionsAuthor: SilverSkyUnternehmensberatungGmbHVenue:FairMadrid/EDates: Apr21–24,2018

OverallImpressionThe28thEuropeanCongressofClinicalMicrobiologyandInfectiousDiseases(ECCMID)inMadridwasvisitedbyroughly12,000microbiologistsandclinicians.Theattachedexhibit,withabout180presentingcompanies,waswellorganizedandattended,howeverwith lesspharma industrypresence (related tonumberofcompaniesand sizes of booths) compared to previous years. In contrast, all big players in the diagnostics space werepresentaccompaniedbymanysmallstart-ups.General SilverSky conclusion: the ID testingmarkethasbecomehighly competitivewithalmost all large IVDplayersofferingPoC-andhigh-through-putpathogenidentification(Roche,QIAGEN,bioMérieuxandothers)aswellthroughsmallercompanieswithpromisingnewbreak-throughtechnologies.Besidessmaller,cheaperandfasterPoCpathogenID,companiesfocusingonrapidphenotypicantibioticresistanceprofiling.

RelevantHighlights

PoCIDTesting:TwoSignificantNewMarketEntriesTwolargeplayersintroducedtheiruniversalPoCsystemsatECCMID2018:1) QIAGENwithStatDx

EarlierthisyearQIAGENacquiredSTAT-Dx,aSpanishprivately-heldcompany.AtthisECCMID, QIAGEN displayed this fully integrated multiplex platform for syndromicdiseasetestingattheirbooth.Theyclaimeasy-to-useassays,suitableforanyclinicalsampletypewithqualitativeaswellasquantitativeresultsfor48-plexreal-timePCRtesting in about one hour. Based on the proprietary DiagCORE technology, thesystemalsoallowsimmunoassay-basedtestingforproteins.

2) BOSCHHEALTHSOLUTIONS/in-housedevelopmentBoschlauncheditsplatformVivalyticwithabigbang–oneofthelargestboothwithspectacular, modern marketing material. Bosch is partnering with other firms forapplyingassaystotheirplatform,aswell fordistribution(currently twocompanies:RandoxLaboratoriesandR-Biopharm).Theall-in-oneopenplatformVivalyticwithsmallfootprintcombinesabroadrangeoftest options in its test cartridge. The device supports end-point PCR, quantitativereal-timePCR,meltingcurveanalysisandmicroarraytechnology.Usingultrasound,samplematerialssuchasfluids,tissuesamplesorsputumcanbeprocessed.Programmablemicrofluidicsallowviruses,bacteriaandfungitobeanalyzedintwoparallelprocessesindependentlyofoneanother.Dependinguponthetestapplication,Vivalyticdeliversresultsin30minutes.ItdoesnotrequireanyperipheraldevicesandsupportscommonstandardssuchasHL7,GDTandPOCT1-A.ThefirsttestsavailableontheVivalyticareRandox’spanels for respiratory and sexually transmitted infections. The URT simultaneously detects 22 viral andbacterialpathogens,whiletheSTItestenablesthedetectionof10viral,bacterialandprotozoanSTIsfromswab samples. R-Biopharmwill offer a new product line specially developed for the Vivalytic platform,providingmultiplexandeconomicallow-andsingle-plexinfectionpanels.

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PoCIDTesting:OtherEstablishedCompetitionResultsofMarketconsolidationandnewproductslaunchedbyestablishedplayers:ABBOTT was well present. After last year’s acquisition turmoil between ABBOTT and ALERE, ABBOTT nowclearlyhasintegratedtheALEREPOCportfolio.ThebrandnameALEREwasstillvisiblealthoughallwasclearlyundertheABBOTTumbrella.ApparentlyABBOTTwasalsodemonstratinganewtechnology,onlyaccessibletoinvitees.TheALEREportfolio(ELISA-based)ispositionedasacosteffectivefirstlinediagnosistoolforinstanceforC.diff.IncaseapositiveresultforC.diffthediagnosismaybeextendedbyamoleculartestforToxA/ToxBgenes.Thisapproachisalreadyestablishedinmanyhospitals.GENMARK was present at the ECCMID as well. Their product offering is not really POC but comes close.Genmarkofferspaneltestingincludingrespiratoryandsepsis.Thee-PLEXsystemisstateofthearttechnology.Genmarkofferssampletoresulttechnology,meaningthatadditionalsampleprepisnotrequired.GENMARK’s(q)PCRisdonewithcapillarysystemsallowingforfastamplificationandrequireslesssamplevolume.Detectionis donewith CMOS technology, for which fluorescence probes are no longer required thus expensive opticsystems are no longer required. Although the systemmay verywell be set-up as a POC system, GENMARKfocusesonhigherthroughputmarkets.Thesystemcanrunin8-24samplessimultaneously.Yet,GENMARK’sbusinessisnotdoingwell.Mainreasonmaybefoundintheveryhighpricingpertest(around250€pertest!)andstillmissing reimbursement formultiplexed testing.Pricing isoftenbasedon theUSmarketwhereCLIAlabsclaimthattheCOGformultiplextestesisaround250US$.MICRONICS: PanNAT® Molecular Diagnostic System is a POC-instrument capable of processing distinctcartridges,eachdesignedtoperformasingleand/ormultiplexednucleicacidamplificationassay.Eachassayis fully integrated into the disposable cartridge that includes all necessary reagents.Only a small volumeofbiological sample is required for assay performance. The PanNAT System provides a sample on – result offanswerinapproximatelyonehour,withnosamplepreparationrequired.Theplatformisuniquelyconfiguredforuseindecentralizedenvironmentsandoffersfullconnectivity.MicronicsisadvancingthePanNATSystemwithafocusonpointofcareinfectiousdiseasediagnostics.

CompanieswithRecentorShortlyUpcomingLaunchesofInterestingProductsMorecompetitiononthehorizon:

• SPINDIAG’scentrifugal-microfluidictestsystemwithPCRdirectlyfromswabsamplesinunder30min,now

focusesonresistancetestingof25mostprevalentdrugs,butisstillquiteawayfromlaunch.• MOBIDIAG launched theCE-markedNovodiag platformwith aC. diff application to be followedbyGTI.

Theirdisposable,asealedcartridgewithmultiplexedR-PCR/arraydeliversresults inaboutonehourwithrandomaccess operation including LIMS connectivity. It is a benchtop, small-sized instrumentwith fourindependentslotsperinstrument.

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• CURETIS–UnyveroLRTtestandplatformisnowFDAapproved,theUSpanelisnotascomprehensiveasits EU version. Smaller low-to-mid-plex system in R&D, expected for commercialization in 2019; newUnyveroCE-IVDDcartridgeforurinarytractinfection.

• ATLAS GENETICS - Their system promoted since years, consists of a small, easy-to-use instrument (ioinstrument)andtest-specific,disposablecartridges(iocartridge),providingtestresultsin30minutes;firstapplicationSTD.Technologyisbasedonelectrochemicaldetectionanddoesnotneedanylaser/optics.

• OPTOLANE. A Korean company focusing on multiplexing and POC presented, the “MENDEL” usingmultiplexPCRforthedetectionofvirusesandbacteria.Theruntimeforsuchassayvaries from25–30minutes.Thedetectionplatformisusing“microarray”technology incombinationwithCMOS.Therefore,multiplexingmay vary from 9 to 22k samples. Since the system uses CMOS technology combinedwithmicroarray, the readout can be done by any USB compatible device like smart phones. The MENDELsystemisabout20x10x10cm,thereforesmallandcompact.CurrentlyOPTOLANEstillrequiresadditionalsamplepreparation,howeverR&D isworkingonasample in resultout technology.Thepanels theywillhavearerespiratory,Sepsis,Tuberculosis,STD.TheMENDELsystemwillbelaunchedin2019.

OthernoteworthyTrends/ObservationsWholeBloodTesting–DiagnosingSepsis–theHolyGrail:DNAe’sLiDiaThe company DNAe presented its’ LiDia platform, based on semiconductorgenomic analysis technology (next generation sequencing (NGS)). LiDia will belaunched in one year from now. The cartridge based test handles whole bloodsamplesforsepsistestinginthreehoursandclaimssensitivityofoneCFU/ml.LiDiacanperformhighlyparallelindividualassaysandNGSonthesametypeofchipandthere is noneed tomeasureoptical signals or use lasers andmicroscopes. Theyclaimlongreadlengths,atthelowcostperbase,andhighoutputperrun,fillingthegapofNGStobeappliedintheclinicalenvironment.Q-LINEAATriD The ASTrID platform, currently under development, will identify pathogendirectlyfromvenousbloodanddeliveranantibioticsusceptibilityprofile intenhours.ThepathogenIDpanelwillcover33pathogensand10pathogengroups,aswellas11resistancemarkers.Thepanelofantibioticsubstanceswillcontainupto48antibioticsandbacterialgrowthorinhibitionreportedasMICvalues.Q-linea´s technology for pathogen detection is based on highly specific padlockprobes and circle-to-circle isothermal nucleic acid amplification technology(C2CA).Thistechnologyallowssubstantiallyhigherdegreeofmultiplexingcapability,comparedtoPCR-basedtechniques.

LowCostMid-/Low-PlexPathogenID–ManyKidsontheBlockAcoupleofsmaller,somenewlyestablishedcompanieswereshowingimpressivelow-costscartridgesystemsforlow-plexing,likeAbacusDiagnostics–a1x2x0,4cmconsumablepartatjustafewcentsonly.

HTSandIDTesting–BecomesCompetitiveAcoupleofvendorsshowedhigh-throughputpathogenIDusingautomatedstations(e.g.MobiDiagbasedonaQiagenplatform).

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NewFunctionalCompetition–NotjustPCRMany companies still focusing on traditional PCR technologies, however interesting functional competitionarises,asrapidphenotype-basedASTorreagent-freeculturing,e.g.:§ Competitive to ACCELERATE, AFFINITY BIOSENSORS’ LifeScale AST provides a rapid phenotype-based

antibiotic susceptibility test instrument utilizing advanced micro-electro-mechanical systems (MEMS)fabricationmethodsanalyzingandquantifyinglivingmicrobes.Itcanaccessuptoo26antibioticsatvariousconcentrationsanddeliversresultsinthreehours.

§ METASYSTEMSHARD&SOFTWAREGMBH:SimilartoAccelerate,theGermandiagnosticscompanyMetaSystemsHard&SoftwareGmbHhassucceedinaugmentingtraditionFISHtechnology.AtECCMIDthecompanypresentedtheMetafer®systemthatenablesmultiplexpathogenidentificationfrombloodculturesanddirectlyfromrespiratorysampleswithinminutes.Inaddition,thecompanyofferssolutionsforautomatedGramstainandTBstainimaging.

§ POCARDDiagnostics promotes direct specimen, fully automated, reagent-freemicroorganismdetection,identificationandenumerationinminutesbasedonphysicalpropertiesofintrinsicfluorescenceusingtheirplatformsP-1000andPS.Thetechnologycapturestheemittedlightfromtheinteractionbetweenphotonsand molecules to detect the pathogens' unique optical properties and subsequently an algorithmdeterminesresults.

§ BIOSPARQ showed their newplatform (under development) based on single CellMALDI-ToF.Using thistechnology allows direct detection of pathogens from the crude sample, thus avoiding costly and timeconsuming sample prep. Up to present, MALDI-ToF may only be used after sample enrichment likeculturing.MALDI-ToFisaveryfastandverycosteffectiveidentificationmethod.Itusuallytakeslessthanaminute and cost are extremely low (Cents). The earning model is in providing access to a MALDI-ToFspectrumlibrarycontainingallspectraofknowpathogens,howeverthesystemisnotabletoidentifyanypathogen not present in the library. The system is built for detection of bacteria, Fungi and otherpathogensandcurrentlynothandlesvirusesalthoughdevelopmentisinprocess.

IncreasingInterestofPharmainFastPathogenIDforStreamliningClinicalTrialsMDxasnoveltoolforpharmatofacilitatepatientenrollment:After the successful implementation of rapid pathogen identification in antimicrobials clinical trials (e.g. forCempra'sphase III trial for its oral drug for community-acquiredbacterial pneumonia)otherpharmaceuticalcompanies become interested in using this approach, e.g. Astellas, MDS, Achaogen, Eumedica, MSD andNabriva.

Summary:Thisyearthefocusofmany(M)Dxcompanies isonPoC.PoCrequiresa fully integratedsystem,reagentandsampleprocessingandresultevaluationinoneandthesamecomponent.Thiswillforsurehaveanimpactonreagentsuppliers.Inaddition,TimetoResultisgettingshorter,meaninglessthanonehour(SampleinResultout).AlsoCMOSisgettingmorepopular.SincetheCMOSisbasedonvoltage/currencymeasurement,theneedfor fluorescenceandoptics isno longernecessary.Thereforesuchsystemsmaybecomeverysmall. Inshort,PoCisonestepclosertorealbreakthrough:FastTimetoResult,SampleinResultoutandminiaturization.

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AboutSilverSkyandourDiagnosticsPracticeMorethan100yearsexpertiseindiagnostics:

E-Mail:info@silversky-lifesciences.com Phone:+49211302708-12 Web:www.silversky-lifesciences.com

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Dr.MirkoStange,Ph.D.Dr.StangeisfounderandCEOoftheSilverSkyGroup.Hisexpertiseincorporatefinance isderived fromhis longstandingpositionasa consultantatMc Kinseyand Droege Comp. As interim managing director of numerous medtech anddiagnosticscompanies,healsohasproventrackrecordinsuccessfullysecuringrisk capital and business building. He gained a PhD in Biochemistry andBiophysicswithafocusoncardiovasculardiseasesfromtheUniversityofNorthCarolina at Chapel Hill and a diploma in chemistry from the Heinrich HeineUniversityDuesseldorf.

SilverSky is a small and highly specialized consultancy focused on diagnostics, medtech and biotech. Itpurposefully restricts its services to corporate financing,businessbuildingand innovation funding. FounderDr. Mirko Stange has put together an energetic, experienced, international and interdisciplinary team toefficiently coverawide rangeof skillsdecisive in the successful founding, expansionandmotivationof lifescienceorganizations.

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