biotron limited (asx:bit) biotech showcase 2018...viral-encoded viroporin proteins • viroporins...

BIOTRONLIMITED(ASX:BIT)BiotechShowcase2018

Forward Looking Statements

This presenta,onmay contain forward-looking statementswith respect to the financial condi,on, results andbusinessachievements/performanceofBiotronLimited(ACN086399144)andcertainoftheplansandobjec,vesof its management. These statements are statements that are not historical facts. Words such as “should”,“expects”, “an,cipates”, “es,mates”, “believes” or similar expressions, as they relate to Biotron Limited, areintended to iden,fy forward-looking statements. By their nature, forward-looking statements involve risk anduncertainty because they reflect Biotron’s current expecta,ons and assump,ons as to future events andcircumstancesthatmaynotproveaccurate.Thereisnoguaranteethattheexpectedevents,trendsorresultswillactuallyoccur.Any changes in suchassump,onsorexpecta,ons could causeactual results todiffermateriallyfromcurrentexpecta,ons.

BiotronLimited

•  Biotron is designing, developing and commercialising a plaUorm ofan,viraldrugswithanovelmodeofac,on–abletotargetawidevarietyofviralinfec,ons

•  Pipelineofprogramsinhighvalue,highneedmarkets•  Progress in clinical leadprogram (BIT225) provides strong valida,on foren,replaUorm

BiotronLimited–SnapShot

BROADPLATFORMWITHNEWCLASSOFANTIVIRALDRUGS

HIV-1ERADICATION HBV&EARLYSTAGEPROGRAMSHEPATITISCVIRUS(HCV)

-  Targe,ngHIV-1inlong-livedreservoirs

-  Phase2trialinprogressduring2017;dosingcomplete

-  NewclassofHCVdrug

-  Phase2completed

-  SeekingpartnershipsinChina

-  Pipelineofearlystageprograms,including:

-  Hepa,,sBvirus

-  Respiratoryviruses

-  Flaviviruses(Dengue)

ROBUSTCLINICALVALIDATION–COMPLETED8CLINICALTRIALSWITHSTRONGSAFETY&EFFICACYOUTCOMES

KeyAchievements2017

•  CommencedPhase2HIV-1clinicaltrialofBIT225andCombina,onAn,retroviralTherapy(cART)inFeb’17

•  DosingwithBIT225/placebocompleted;datapending(an,cipated1Q18)

•  Demonstratedsignificantandacceleratedreduc,oninHIV-1viralloadfollowingaddi,onofBIT225inhumanisedmousemodelofHIV-1infec,oninFeb‘17

•  IndependentNaturepublica,onvalidatedBiotron’sapproachoftarge,ngHIV-1inmacrophagesasakeystepinHIV-1eradica,oninMay’17

•  AppointedaCorporateAdvisorforChina–assis,ngwithexecu,ngHCVregionalpartneringstrategyinJune‘17

•  Raised$1.56millionviarightsissueinJune‘17

•  Received$1.6millionR&DtaxrefundinNov‘17

HIV-1EradicaTonCurrentdrugsdonoteradicateHIV-1virus

WhyisHIV-1eradicaTonnecessary?•  Long-termhealthimplica,onse.g.HAND,immuneac,va,on,drug-drug

interac,ons•  Costoftreatment

•  ~$20billionp.a.worldwide•  Majorburdenonhealthcaresystems

BIT225haspotenTaltobeusedincombinaTonwithotherdrugsto

eradicateHIV-1reservoirs

•  HIV-1remainshiddeninreservoirs,leadingtochronic,life-longinfec,on•  Invisibletobody’simmunedefenses•  Notsensi,vetoan,-HIV-1drugs

•  Newmodeofac,onsdrugsareneededtoeradicateorcureHIV-1infec,on

MarioStevensonScien.ficAmerican299,78-83(2008)

CurrentDrugsDoNotEradicateHIV-1

MacrophagesareKeyHIV-1Reservoirs

StudypublishedinNatureMedicineinApril2017confirmedthatmacrophagesarekeyviralreservoirs

•  BIT225inhibitsassemblyandbuddingofnewvirusinmacrophagereservoirs

•  Phase1b/2atrial(004)demonstratedthatBIT225canreduceHIV-1levelsinmacrophagecellsinvivo,parallelinginvitrostudies(Wilkinsonetal,JAn,microbChemother.2015)

•  Phase2trial(009)inprogress(BIT225incombina,onwithART)during2017

BIT225TargetsHIV-1inReservoirCells

A B

(A)UntreatedControls (B)BIT225treatedcells

BIT225–ProvenClinicalAcTvityAgainstHIV-1•  BIT225-004:Phase1b/2arandomised,placebocontrolled,double-

blindtrial–  21pa,ents,HIV-1posi,ve,treatment-naïve;10daysdosing

withBIT225(monotherapy)•  ResultsdemonstratedthatBIT225:

1.  TargetsHIV-1inbloodreservoircells,andsignificantlyreducesvirusinthesecells

2.  Crossestheblood-brainbarrier,openingupthepossibilityoftreatmentofAIDS-relateddemenTa

2.  Reducedmyeloid-specificimmuneacTvaTonmarkersduringtrial

2 4 6 8

10 12 14 16

5 10 15 20 25

HIV-1Re

plica,

on(p

g/20

0uL)

TimeinCo-culture(days)

BIT225Placebo

PotenTalroleforBIT225:-  AddiTontocurrentARTtoeradicatekeyreservoirs,impacTngimmuneacTvaTon-  Keycomponentofcure/eradicaTonstrategies

HIV-1EradicaTon:BIT225-009Trial

•  36HIV-1+ve,treatment-naïvesubjectscommencingART•  Randomised2:1(drug:placebo)

BIT225orplaceboaddedtoART

•  BIT225orplaceboaddedtoARTforfirst12weeksoftreatment•  Read-out

•  Impactonviruslevels;reduc,onofimmuneac,va,onmarkers•  Fullyrecruited;completeddosingwithBIT225/placebo.AnTcipatedatain1Q18

Biotron–NewApproachtoAnT-ViralDrugDevelopment

•  Coreexper,seisdesignanddevelopmentofanewclassofan,viraldrugstarge,ngviral-encodedviroporinproteins

•  Viroporinsarepresentinwiderangeofviruses:Influenza(M2),HIV-1(Vpu),HCV(p7),DengueandWestNile(Mprotein),SARS(Eprotein)andothers

•  BroadplaUorm:

•  Rapid,proprietaryprimarybacterialcell-basedscreeningassaysfortargetproteins

•  Focusedlibraryofcompoundsthattargettheseviralproteins

•  Pipelineofinternally-generated,first-in-classsmallmoleculeviroporininhibitorsforkeymarkets

Viroporins

•  Smallhydrophobicproteinswithionchannelac,vity

•  Formhydrophilicporesinhostcellmembranes

•  Keystagesoftheviralcyclesuchasvirusuncoa,ng,transportandmatura,onareion-influencedprocessesinmanyviralspecies

•  Crucialforviralpathogenicityduetoinvolvementinvariousstepsofviruslifecycles

•  IdealtherapeuTctargets;exemplifiedbyBiotron’sHIV-1program(BIT225)

NatureReviewsMicrobiology10,563-574

UnlockingValueforOtherVirusTargets

Libraryofcompoundsdesignedtotargetviroporinsfoundinsomeviruses:Ini,ally>250compoundsdesignedandsynthesised;librarynow~350OTHER“HITS”INLIBRARYinclude:•  InfluenzaAandB•  Hepa,,sBvirus(HBV)•  Coronaviruses(IncludingSARS)•  Epstein-Barrvirus(EBV)•  Zikavirus•  Denguevirus•  Herpesviruses•  BKvirus

X-axis:compoundIDY-axis:virusZ-axis:strengthofhit

UnlockingValueforOtherVirusTargets

Biotron’sViroporinapproachenablesthetarge,ngofawiderangeofviraldiseases;examplesinclude:•  RespiratoryVirusessuchasRespiratorySyncy,alVirus(RSV),Influenza,&Coronaviruses(leading

causeof“commoncold”)•  FlavivirusessuchasZikaVirusandDengue•  TransplantvirusessuchasBKvirus•  EpsteinBarrvirus(EBV)-par,cularinterestinAsiawhereitiscausa,veagentofNasopharyngeal

Carcinoma Biotron’sViroporin-targeTngplahormhasthepotenTaltobecomeanimportanttoolin

thedevelopmentofanTviraltherapies

HepaTTsBVirusProgram•  Hepa,,sBvirus(HBV)therapeu,cspacehassignificantinterestfrompharma&biotechcompanies

•  ScreeningofBiotron’scompoundlibraryhasiden,fiedseveralcompoundswithac,vityagainstHBV

•  ScreeninginHepG2andAD38celllines,aswellasstudiesinprimaryhumanhepatocytes(PHH)

•  InvitrodataincludesevidenceofreducTonofindustryrecognisedmarkers,includingcccDNA

•  Biotroncompoundsappeartohaveanovelmechanismofac,on•  Poten,alforuseincombina,onapproachestotreatmentofHBV

•  ExpandsBiotron’spartneringopportuni,es–poten,alforearlystageco-development/collabora,onagreement

DengueVirusProgram

•  2.5billionpeople(40%worldpopula,on)liveinareasatriskofDengue

•  ~100millionpeopleinfectedyearly

•  Aleadingcauseofillnessanddeathintropicsandsubtropics

•  Transmissionisbymosquito;mostpreven,onprogramstargetthevector

•  NoapprovedDengue-specifictherapeu,cdrug

•  Vaccinetrialshavehaddisappoin,ngresults

•  Biotronistarge,ngDengueMprotein–SimilartargettoHIV-1/VpuandHCV/p7

•  Severalcompoundswithpromisingac,vityhavebeengenerated;testsareon-going

•  Poten,alforpan-Flavivirustherapeu,c

www.sciencenews.org

HCV–RemainsanOpportunity

•  ThenewHCVdrugsmaycausereac,va,onofHBVinHCV/HBVcoinfectedpa,ents

•  ResultedinUSFDA“BlackBox”WarningonnewHCVdrugs

•  30millionHCV-infectedpeopleinChina,comparedto3-5millioninUSA

•  93millionchronicallyinfectedwithHBVinChina,comparedto2.2millioninUSA

•  HighHCV/HBVco-infec,onrateinChina(es,matedtobe10million)

•  Reac,va,onofHBVhaspoten,altobeamajorhealth&economicissueinChina

•  BIT225hasbeenshowninclinicaltrialstosignificantlyimproveclinicaloutcomeinHCVGT1-infectedpa,entsincombina,onwithInterferon&Ribavirin(IFN/RBV)

•  IFN/RBVhaveseveralpoten,aladvantagesovernewHCVdrugsinsomeseyngs

•  IFN/RBVissignificantlycheaperthanthenewHCVdrugs

•  HBVreac,va,onislesscommonandlesssevereinHCV/HBVco-infectedpa,entswithIFN/RBV

•  SeekingpartnershipsforBiotron’sHCVprograminChina

CommercialisaTonandPartnering

•  HIV-1Program-Significantvalueinflec,onpointsaroundHIV-1programdataexpectedin2018

•  HCVProgram-BIT225par,cularlywellsuitedtoAsia,withhighnumbersofHCV-infectedpa,entsincludingahighpropor,onofHCV/HBVco-infectedpa,ents

•  Earlystagecollabora,onopportuni,esforpre-clinicaltargets,suchas:

•  Hepa,,sB

•  Dengue

•  Addi,onaldevelopmentcollabora,onpoten,alfor“other”pharmatargets

•  Seekingpartnersforindividualtargetsoren,replaUorm

BoardMichaelHoy Non-execu,veChairman

MichelleMiller ManagingDirector

SusanPond Non-execu,veDirector

RobThomas Non-execu,veDirector

CorporateSnapshot

KeyFinancialMetricsTickerCode ASX:BIT

SharePrice(09Jan18) A$0.03

Marketcapitalisa,on A$11.4million

12MonthTradingRange A$0.016–0.046

SharesOutstanding 392million

CashPosi,on(09/2017) A$0.83million*

*ExcludesA$1.6mR&DtaxrebatereceivedinNov‘17

•  SpunoutfromJohnCur,nSchoolofMedicalResearchattheAustralianNa,onalUniversityin1999

•  ListedonASXinJan2001(ASX:BIT)

•  HeadquarteredinSydney,Australia

BriefBiotronOverview

InvestmentHighlights

PorholioofpatentsandpatentapplicaTonsdirected to theCompany’s anT-viraldrugporholio

STRONGINTELLECTUALPROPERTYPOSITION

TargeTngviroporinproteinswitharapidscreeningproprietaryprimarybacterialcell-basedplahorm-alibraryofover350compoundswithacTvityagainstarangeofviruses.

NOVELANTIVIRALPLATFORM

ClinicalandPreclinicalprogramsinindicaTonswithhighunmetclinicalneedorlargepaTentpopulaTonssuchasHIV-1,HCV&Dengue,HBV,Zika&Influenza

BROADANTIVIRALPIPELINE

Completed7humanClinicalTrialswithpromisingsafetyandefficacyoutcomes

ROBUSTCLINICALVALIDATION

15 20

REPORT ANNUAL

BIOTRON

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DrMichelleMillerManagingDirector+61412313329mmiller@biotron.com.auwww.biotron.com.au