ThecommercialisationofSCENESSE®isalongawaiteddreamofmanyscientistsandpatients
aroundtheworld.ForClinuvelitmarksthestartofanewphase.
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Australiaisthebirthplaceofagreatnumberofinventionsandinnovations.Asof24October
SCENESSE® afamelanotide16mg ,developedfrombenchtobedbytheAustralianbased
companyClinuvelPharmaceuticals,canbeaddedtothelist.IntheprocesstheCompany
optimised thechemistry,developedtheformulation,identifiedtheindications,andintroduced
theproducttothewidermedicalcommunity.SCENESSE®isthefirstcommerciallyavailable
systemicphotoprotectant forthetreatmentofthemostextremeformoflightandUVintolerance:
erythropoieticprotoporphyria,EPP.
Itisveryraretodevelopanovelmolecule,formulationandindication;inthiscaseithasbeen
achievedwitharelativelysmallteamfrominceptiontocommercialstage.
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Warningagainstspeculativestatementsthatmaybemadeattoday’sAGM,thepublicisrequested
toreadtheForwardLookingor‘SafeHarbour’Statement.
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Therearefoursectionsbeingdiscussedtoday.
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Clinuvel’sbusinessplanwaspresentedin2005,consistingofinvolvementandengagementwith
thetopacademicsworldwide.
Nearly10yearslatertheleadingacademiccentersinthefieldsofinteresthavebeeninvolvedin
thedevelopmentofSCENESSE®.TheirfeedbackisincorporatedinClinuvel’sclinicalprograms.
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Insomedisorders,patientorganisationsarefundamentaltothesuccessofaclinicalprogram,
sincetheyrepresentthepatients’voices.
Patientorganisationswilloftencommunicatethepatients’feedbackafteratrialcompletion,the
drawbacksofstudydesignsandbetherepresentativebodytoelucidatetheneedtotreatthe
disease.
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Clinuvelhasbuiltupconsiderableregulatoryknowhowovertheyears,spanningseveral
continentsandmanycountries.
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OverallClinuvel’svalueliesintheaggregateelements,IP,specificknowhow,itsregistration
dossierandmanufacturingprocessesforitsfinalproduct.
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Ittooknearly10yearsunderClinuvel’smanagementtodevelopSCENESSE®toacommercial
product.Thisisthefirsttimeasystemicphotoprotectant ofthemelanocortin familyhasobtained
regulatoryapproval.
Theplanningtofurtherdevelopandcommercialise newmarkets,indicationsandfollow‐on
productsisbeingdiscussed.
Aclearsequenceneededtobefollowed withintheuniquelimitationsofClinuveltobeableto
executeonourcommercialplans,aswillbeoutlinedoverthecomingslides.
Thetableindicatestheprobabilityofanewdrugreachingmarketingauthorisationasitenters
eachstepofthedevelopmentprocess.
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TheintegralvalueofClinuvelstartswithSCENESSE®,thefirstdrugusedinanextremedisorder
causedbydaylight,UV.
Theinitialrisksinthisbusinesswerehigh.
AdditionallytherewereuniquerisksassociatedwithClinuvel,someundulyassigned,somedue
toillegitimatemarkets,othersduetothelackofunderstandingduringthedevelopmentofa
noveltechnologywithanewmodeofaction.
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ErythropoieticprotoporphyriawastargeteditwasunderstoodthatSCENESSE®couldbeof
therapeuticbenefit.
Additionalcriteria,suchashighunmetmedicalneed,noalternativetreatmentandmarket
exclusivity,wereessentialforthechoiceofEPPasClinuvel’sleadindication.Patients’needand
demandweretheprominentreasontoprogressSCENESSE®intheclinic.Clearlytherewasno
competition.
EPPispredominantlyseeninCaucasianpopulations FitzpatrickskintypesI‐III .
EPPisthemostextremeformoflightdeprivationandpatientssufferacutepainwhenskinis
exposedtocertainwavelengthsoflightandUV.Itisalsoararedisease,witharecognisedneedto
treatfromregulatoryauthoritiesintheformoforphandrugdesignations.
WithapositivevotefromtheEuropeanMedicinesAgencyonMarketingAuthorisation,Clinuvel
nowhasaproofofconceptformedicinalphotoprotectionwithSCENESSE®,allowingthe
Companytoprogresstoacommercialphaseandpursueexpandedprogramswithitstechnology.
Progresswouldonlyoccurwhenreimbursementwassecured.
In2010theCompanyreceivedthefirstproofofsupportfrompayors,withtheItaliangovernment
agreeingtoreimbursesupplyforadultEPPpatients.Thisprogramhascontinuedfornearlyfive
years.Furtherproofarrivedin2012withinsurersinSwitzerlandagreeingtoreimbursethedrug.
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OurEuropeanMarketingAuthorisationprovidesconfidencetoexpandtheprogramintobroader
markets,withvitiligothefirsttarget.
Despiteitshighprevalenceandsignificantimpactonpatients,therearenofullyeffective
therapiesforvitiligo.TodatethemainstayoftreatmenthasbeennarrowbandUVBlight,an
expensivetherapyrequiringintensivecommitmentfrompatients.Topicalandsystemicsteroids
areprescribedoff‐labelinvitiligo,buttheireffectivenessvaries.
Vitiligoisseenashavingthegreatestimpactonpatientswithdarkerskin– Fitzpatrickskintypes
IV‐VI– forwhomthediseaseisoftendescribedascausinganidentitycrisis.Earlyclinicalresults
withSCENESSE®asanadjuncttonarrowbandUVBhaveindicatedthattheclinicalbenefitis
largerandfasterinthesepatients.TheCompanyseesitasethicallynecessarytopursue
treatmentforthesepatientgroups.
Asaresult,theCompanyhasdifferenttargetmarketsforitstwoleadindications,treatingEPPin
CaucasianpopulationsintheNorthernHemisphere,aswellasalimitedpopulationinJapan,and
treatingvitiligoindarkerskintypesinNorthAmerican,AsiaandAfrica.
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Inparalleltothevitiligoprogram,theCompanywillseekbroaderapplicationofSCENESSE®,
withacommitmenttofocusingonpaediatric EPPpatients.
RecentadvancesinourunderstandingandIPwillallowustoexpandourofferingto
complementarytherapies.Itmustbenoted,however,thatthiswasonlypossiblehavingproven
theconceptofmedicinalphotoprotectionandthesafetyandefficacyofSCENESSE®.
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Clinuvelwillnowbeabletocapitaliseonitsin‐houseexpertiseandleadthefieldof
melanocortins,withtopicalformulationsofalpha‐MSHanaloguesthenextstepinour
development.
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ThefinancialsofClinuvelreflectthequarterlystatementsandannualfilings.TheCompanyhas
beendebtfreeandmaintainedaconsistentburnoverthepastyears.
Purposefully,CUVrequiredraisedcapitalinninerounds,wherebyitisstressedthatinthelast
threeissuancescapitalwasraisedatpremium.
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TheCompanyhassoughttomaintainabalancedregister.
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TheCompanyhasinvestedthemajorityofitsclinicalexpenditurestodateintheleadprogram,
EPP.
Expensesincludenon‐cashadjustments.
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TheCompanyisrapidlytransformingfromapureR&Dfocusedtoacommerciallydrivenentity.
RelevantstaffarebeinghiredtosucceedintheEuropeandistribution.
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TheprogressofEuropeanregulatoryreviewfrombeginningtoapprovalwasgradual.Asmore
informationaboutmodeofaction,disease,physicians’experiencesandpatients’benefitbecame
known,theEMA arrivedatafullunderstandingoftheclinicaluseandbenefitofSCENESSE®.
Drugsubstance:Aminoacidsandimpurities
Drugproduct:dosageform,releaseinconsistently,manufacturingmethod
Pharmacology:pharmacokineticandpharmacodynamic relationship,modeofaction
Toxicology:melanoma,CNSeffects,irreversiblenaevi
Pharmacology:modeofaction,dosingrationale
Clinicalsafety:pigmentation,accumulation,prolongeddruginblood,CNS,eyes
Clinicalefficacy:rationaleofdrug,evaluationofefficacy
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TheendpointsfrombothstudiesshowhowSCENESSE®wasclinicallyevaluatedoverfive
studiesinvolvingaround350patients.
DecisionstocontinuetheEPPprogramwerebasedonbothtrialresults– safetyandefficacy– as
wellasongoingregulatory,physicianandpatientfeedback.Overthecourseoftheprogramwe
sawincreasingsupportfromthesecommunities.
ProgramsinItaly 2010 andSwitzerland 2012 havegivenanindicationofthedrugunder
‘conditionsofuse’, andfiveyearsofspecialaccessscheme SAS data,with115patientsreceiving
treatmentundertheseprogramsoverthepast12months.
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EPPisapoorlyunderstooddisorder.DuetothefearofdebilitatingskinreactionstoUV/light,
patientsbecomedeprivedoflight exposure andtheabilitytoleada‘normal’life.FormostEPP
patientsthediseasedictatesmanylifedecisionsandcanleadtoanxietyanddepression.Thelack
oftreatmentorviablepreventionforEPPreactionstodatemeansmanypatientsareforcedto
leadindoorandwithdrawnlivesorrisksevereburnsstartingaphototoxicreactionthatmaylast
weeksdependingontheindividual.Insomecasesitleadstohospitalisationanddistress.
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Independentlyevaluatedagainstotherdisorders,EPPisconsideredtobeasevere,chronic
disorderinneedofannualtreatment.
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Reviewingthepharmaceuticallandscape,recenttrendsreflectapremiumfororphandrugs.
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InbenchmarkingSCENESSE®againstotherorphandrugsdeveloped,andviewingreturnson
investment,anumberofobservationsarebeingmade.
ThemostrecentnumbersondrugdevelopmentareUS$1bfortheentireprogram,Clinuvel’s
A$120Mholdsupwellasoneofthemosteconomicalprogramsintheorphandrugfield.
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Intheclinicalphaseandcommercialphasebothonoverseas’marketsandNasdaqtherearefew
‘orphandrug’pharmaceuticalsatUS$200M.
BenchmarkingCUVagainstpeersprovidessomeinsightinmarketvaluations.
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ItalyandSwitzerlandhavegivenmorethantwoyearsof‘conditionsofuse’andfiveyearsof
specialaccessscheme SAS datainEPPpatients.Thetableshowsreimbursementfor
SCENESSE®byinsurersandregionalauthoritiesinthesetwocountries,andinrecenttimes,also
fromotherEuropeannations.
Thedrughasbeenwelltolerated.Ofthosepatientswhohavediscontinuedtreatment,the
majorityhavedonesoforreasonsunrelatedtotreatment.
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EUdistributionisinpreparationfollowingtheEMA ‘approval’on23October2014 morning24
OctMelbourne .
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ThefirstkeystrategicmarketsforEPPhadbeenidentifiedbyClinuvel.Themarketsinblueare
underconsideration.
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ModellingEPPbyanalystsandpeerspresumesanumberofvariables.Oncepricingisestablished
inEU,anadequatemarketsizecanbeestimated.
InClinuvel’scasethe5yearsofexperienceduringthe‘SpecialAccessSchemes’providesdatafor
modelling.
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VitiligoattractsmuchattentioninNorthAmericagiventhemagnitudeoftheclinicalproblem
mostapparentinpatientsofcolourduetothecontrastbetweenvitiligoandnon‐vitiliginous
lesions.
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Penetrationratesinalowcasescenarioisbeingdiscussed,giventhedemographicsandpatient
populationknown.
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Patientsofskincolourwholosetheirpigmentationoftenseeagradualprogressionofdisease.It
causesmuchdistressandsenseofhelplessness.Patientswholosealargesurfaceareaof
pigmentationpresentsuchasthepatientinDay0 lefthandside .Thispatient’sde‐pigmentation
isgeneralisedovertheentirebodysurface.Typicalislossoftotalpigmentationofhandandfeet.
Repigmentation oftheseareasisaparticularclinicaldilemma.
Inthispatienttotalrepigmentation wasachieved,wherebythefeetarestillde‐pigmented,but
someproximaltodistalrepigmentation isstarted.
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Closeuprevealsthefollicularpatternrepigmentation‘islands’throughouttheepidermis.The
Day176imagesareparticularlyimportantasrateanddepthofrepigmentationisassessed.
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Afurthercloseupshowsindividual‘islands’ofpigmentdeveloping.
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Theseislandsrepresentthemelanocytestemcellsnearahairfollicle.Thematurationof
melanocytesenablesthefirstpigmentationtobecomevisible.
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Clinuvelisknownasthecompanywhichtreatsvitiligoindarkerskinpopulations,wherebyVIP
catchtheeyeoftheimagination.
ManyoftheindustrypublicationsfocusonthepositiveresultsfromCUV102.
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SupportfromClinuvelBoard,investorsandstaffhavebeenfundamentaltoClinuvel’ssuccess.
ThegreatestassetsoftheCompanyareitspeople.
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