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Makingbonemarrowtransplantationssaferandmoreeffective
Patientspecificcell-basedimmunotherapyproducts,asadjunctivetreatmenttohaploidenticalhematopoieticstemcelltransplantation(HSCT),forthetreatmentofbloodcancersandinheritedblooddisorders
Companypresentation,May182017
Amsterdam,TheNetherlandsEuronext(KDS)
Disclaimer
Theseslidesandtheaccompanyingoralpresentationcontainforward-lookingstatementsandinformation.Forward-lookingstatementsaresubjecttoknownandunknownrisks,uncertainties,andotherfactorsthatmaycauseourorourindustry’sactualresults, levelsoractivity,performanceorachievementstobemateriallydifferentfromthoseanticipatedbysuchstatements.Theuseofwordssuchas“may”,“might”,“will”,“should”,“could”,“expect”,“plan”,“anticipate”,“believe”,“estimate”,“project”,“intend”,“future”, “potential”or“continue”,andothersimilarexpressionsareintendedtoidentifyforwardlookingstatements.Forexample,allstatements we makeregarding(i)theinitiation,timing,cost,progressandresultsofourpreclinicalandclinicalstudiesandourresearchanddevelopmentprograms,(ii)ourabilitytoadvanceproductcandidatesinto,andsuccessfullycomplete,clinicalstudies,(iii)thetimingorlikelihoodofregulatoryfilingsandapprovals,(iv)ourabilitytodevelop,manufactureandcommercializeourproductcandidatesandtoimprovethemanufacturingprocess,(v)therateanddegreeofmarketacceptanceofourproductcandidates,(vi)thesizeandgrowthpotentialofthemarketsforourproductcandidatesandourabilitytoservethosemarkets,and(vii)ourexpectationsregardingourabilitytoobtainandmaintainintellectualpropertyprotectionforourproductcandidates,areforwardlooking.Allforward-lookingstatementsarebasedoncurrentestimates,assumptionsandexpectationsbyourmanagementthat,althoughwebelievetobereasonable,areinherentlyuncertain.Allforward-lookingstatementsaresubjecttorisksanduncertaintiesthatmaycauseactualresultstodiffermateriallyfromthosethatweexpected.Anyforward-lookingstatementspeaksonlyasofthedateonwhichitwasmade.Weundertakenoobligationtopubliclyupdateorreviseanyforward-lookingstatement,whetherasaresultofnewinformation,futureeventsorotherwise,exceptasrequiredbylaw.Thispresentationisnot,andnothinginitshouldbeconstruedas,anoffer,invitationorrecommendationinrespectofoursecurities,oranoffer,invitationorrecommendationtosell,orasolicitationofanoffertobuy,anyofoursecuritiesinanyjurisdiction.Neitherthispresentationnoranythinginitshallformthebasisofanycontractorcommitment.Thispresentation isnotintendedtoberelieduponasadvicetoinvestorsorpotentialinvestorsanddoesnottakeintoaccounttheinvestmentobjectives,financialsituationorneedsofanyinvestor.
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Kiadis:companyataglance
• BasedinAmsterdam,TheNetherlands
• NewCEOandCOOaddbusinessandsupplychaintrackrecord
• Strongteam,exCrucell,J&J,Organon,Wyeth,McKinsey,DSM,Sanquin
• EuronextAmsterdam/Brussels,listedin2015raising€35M
• Majorshareholders:LSP,DraperEsprit,Alta
• Analystcoverage:KBCSecurities,Kempen,Edison,RothCapital
• Marketcap:€115M(15May2017)
• YE2016cash:€14.6million
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TEAM
SHARE-HOLDERS
FINANCIALS
Kiadis:neartermandlargeopportunityinHSCT
• IPprotectedpatientspecificcelltherapyproductasadjunctivetohaploidenticalhematopoieticstemcelltransplantation(HSCT)
• OrphanDrugdesignationsUSandEU;targetpopulation28,700patientswithbloodcancersandinheritedblooddisorders
• PhaseII1yeardatasuperiortoliteratureforalternatives,includingPTCy/BaltimoreandZalmoxis(Molmed,EMAapproved)
• FiledwithEMAbasedonPhaseII,(conditional)approvalexpectedH22018;PhaseIIIagainstPTCy/BaltimoreinitiatedforFDA
• Efficient5daymanufacturing,withoutgeneticengineering;easilyintegratedintoexistingtransplantationcenterprocesses
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BLOCKBUSTER POTENTIAL
SUPERIOR DATA
IN EU MARKET EXPECTED 2019
EFFICIENT SUPPLY CHAIN
UNIQUE PLATFORM
AllogeneicHematopoieticStemCellTransplantation(HSCT)
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Harvestingofdonorstemcellsandimmunecellstoengraftnewbloodand
immunesystem
Conditioningofpatient to
destroydiseasedbloodandimmune
system
Hematopoieticstemcelltransplantation(HSCT):replacetheorgancausingthediseasewithahealthonefromadonor
AllogeneicHSCT:mostlybloodcancers
6Passweg BMT2017(Europe)
Bloodcancers
• Acuteleukemia• Chronicleukemia• Lymphoma• Multiplemyeloma• MDS
Inheritedblooddisorders
• Thalassemia• Sicklecellanemia
Inheritedimmunedisorders
• SCID• Wiskott-Aldrich
Trade-offwithHSCT:needmatureT-cells,yetavoidGVHD
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MaturepotentT-cellsneededforimmediateprotection
MaturepotentT-cellsattackpatienttissue
Reconstitutionofimmunesystemfromdonorstemcells:• NK/B-cells:1-2months• T-cells:6-12months
InfusionofHSCTgraft
GraftVersusHostDisease(GVHD)
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AcuteGVHD
• GradeI/II:manageable
• GradeIII/IV:lifethreatening
ChronicsevereGVHD
• Increasedriskofinfections
• Severelydebilitating,persistsyears
Affectedorgans:• Skin,mouth,eyes,liver,
gastrointestinaltract,lungs
Manifestations:• Rash,scleroderma,ulceration,
erythema,cirrhosis,immunodeficiency
Treatment:• Immunosuppression(e.g.
corticosteroids),anti-infectives
Matureallo-reactiveT-cellsfromdonorattackantigenicallyforeignepithelialtissuesofpatient(MHCclassIIproteins)
HaploidenticalHSCT:donorsavailable,ifGVHDcontrolled
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65%37,000waiting,ofwhich13,000inUS,
manyneverfinddonor
Availability
Historicalstandard:Geneticallymatchedrelated/
unrelateddonors,tolimitGVHD
95%Allparentsandchildrencanbe
donor
Availability
Emergingalternative:Half-matchedhaploidenticaldonors,
yethighinherentGVHDrisk
Moreallo-reactiveT-cells
Source:Lancet2015;DefinedHealth2013
GrowthinhaploidenticalHSCT,duetoPTCy/Baltimore
10
1985 1995 2005 2015
1,000
2,000
3,000
4,000
0
MatchedrelatedMRDMatchedUnrelatedMUDCordbloodHaploidenticalHID
1995 2005 2015
9,000
1,000
3,000
5,000
7,000
0
MatchedrelatedMRDHaploidenticalHIDMatchedunrelatedMUDcordblood
Source:EBMT,CIBMTR
Growthinhaploidenticalatexpenseofmatchedunrelatedandcordblood
US Europe
StrategytoGVHD
HaploidenticalHSCT
Adjunctivedose(afterHSCT)
GVHDtreatment/prophylaxis
ATIR(Kiadis) Prevention(exvivo)
T-celldepleted(‘Safe’HSCT)
Subset ofT-cells:depletedofGVHDcausingT-cells(‘Safe’T-cells)
Noprophylacticimmunosuppressantneeded
Zalmoxis(MolMed)BPX-501(Bellicum)
Treatment(exvivo/inpatient)
T-celldepletedT-cellsgeneticallyengineeredwithsuicideswitch
IfGVHDoccurssuicideagentinfusedtoeliminateT-cells(ganciclovir,rimiducid)
PTCy (‘Baltimoreprotocol’)
Treatment(inpatient)
T-cellreplete(stemcellsandallimmunecells)
None
Post-TransplantCyclophosphamide(PTCy)&immunosuppressanttocontrolalloreactiveT-cellresponse
EnablinghaploidenticalHSCT:depleteT-cellsthatcauseGVHD
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ATIR:adjunctiveinfusionof‘safe’T-cells,28-32dayspostHSCT
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Step 1 (Day 1–4)
Patient cells inactivated by radiation
Healthy donor
Patient
Immune cells are collected and mixed
Step 3 (Day 5)Step 2 (Day 5)donor
patient
`
InactivateT-cellsfrompatientbyradiation
``
ATIR:remainingdonorimmunecells,infusedonday28-32afterHSCT
AddTH9402*,whichaccumulatesonlyinactivatedT-cells,duetolackofPgP pump
function
GVHDcausingT-cellsdepletedby‘causingGVHDexvivo’;immunecellsagainsttumorandinfectionsretained
*TH9402– proprietaryselectiverhodaminederivative,modifiedtobecomecytotoxicundergreenlight
Mixpatient&donorimmunecells:alloreactiveT-cellsbecomeactivated(MixedLymphocyte
Reaction)
Exposetogreenlight,TH9402becomestoxic:activated
alloreactiveT-cellsarekilled
Knowhow,issuedpatents(till2021),pendingpatents(estimatedtill2036)
Pipeline:ATIR101forbloodcancers,ATIR201forthalassemia
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ATIR201Inheritedblooddisorders
ATIR101Bloodcancers
PhaseI/II PhaseII PhaseIIITrialdesigns- CR-GVH-001(dosefinding)
- CR-AIR-006(historiccontrol)
- CR-AIR-007(efficacy)
- CR-AIR-008(2nd dose)
- CR-AIR-009(randomized,controlled)
- Adultacuteleukemia
- Myeloablativeconditioning
- CD34+stemcell
- CR-BD-001(dosefinding)
- Pediatric βthalassemia
- Myeloablativeconditioning
- αβ T-celldepleted
ATIR101:potentmatureT-cells,yetlowGVHD(1yr)
• noacutegradeIII/IV• 3acutegradeII(13%)• 1chronic(4%)
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ImprovedOverallSurvivalwithATIR
61%
21%
007:CD34+plussingledoseATIR
• Openlabelsinglearm2013-16• 23patients:AML/ALL• 4sitesinCanadaandEU
006:CD34+
• Historicalobservationalcohort2006-13• 34patients,matchedindications/sites• BasedonEMAscientificadvice
CD34+withATIR(007)
CD34+withoutATIR(006)
LowGVHDrelatedtoATIR
ATIRdepletioneffective:potentT-cellsprovidingprotection,yetlowGVHD
ATIR101:filingEMAMarketingAuthorizationApplication(MAA)
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ATMPcertificateApril2015forqualityandnon-clinicaldata
OrphanDrugDesignation(allHSCTindications)
Pediatric InvestigationPlanagreedwithEMA
RapporteursacceptedPhaseIIdatawithhistoricalcontrolforfilingandreview
EMAMAAsubmittedApril2017basedonPhaseII(likeEMAapprovedZalmoxis)(Conditional)approvaltobeexpected2nd half2018
ATIR101:superiorvsEMAapprovedproductZalmoxis(1yr)
HigherSurvival LowerRelapse
9%
30%
42%
20%
Relapse NonRelapseMortality
61%
51%
OverallSurvival
4%7% 6%
AcuteGVHDIII/IV
ChronicGVHD
LowerGVHD
Note:NOTbasedonrandomizedcontrolledtrials*CHMPAssessmentreport(exceptforaGVHD III/IV);CD34+HSCT;74%AML;10%ALL;16%MDS/NHL/HD,
ATIRPhaseII(007),n=23
Zalmoxis(Molmed)PhaseIIdatainEMAfiling,n=36*
Zalmoxis:EUconditionallyapprovedJune2016basedonPhaseIIdataandmatchedhistorical
control
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0%
Objectives:demonstratesuperiorclinicalbenefitandcollectpharmacoeconomical data(cost,daysinhospital,incidenceofsevereinfectionsandqualityoflife)
ATIR101PhaseIII(009)initiated:ATIRversusPTCy/Baltimore
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R
RandomizedControlled(1:1)
Kiadisprotocol:CD34+HSCT+singledoseATIR101
PTCy/Baltimoreprotocol:post-HSCTcyclophosphamide&immunosuppressant
Primaryendpoint:GVHDandRelapseFreeSurvival(GRFS**)
Secondaryendpoints:OS,ProgressionFreeSurvival,RelapseRelatedMortality,TransplantRelatedMortality
Eventdriven:Primaryanalysisat93GRFSevents
195patients*withacuteleukemia45sitesinUS,CanadaandEU
ProtocolandGRFSasendpointalignedwithEMAandFDA(EndofPhaseIImeeting)Trialapprovedinseveralcountries,liningupsites
*Designedandpoweredfor20%differenceinGRFS**SurvivalwithoutchronicGVHDrequiringimmunosuppression,acutegradeIII/IVGVHDandrelapse
ATIR101:superiorGRFSvsliteratureforPTCy (1yr)
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HigherGVHDandRelapseFreeSurvival(GRFS)
Survivalwithout:• ChronicGVHDrequiring
immunosuppression• AcutegradeIII/IVGVHD• Relapse
Compositeendpoint:survival,qualityoflife,futureprognosis
Note:NOTbasedonrandomizedcontrolledtrials*Solh 2016(Atlanta;DRInormalizedGRFS30%;n=128);McCurdy2017(JohnsHopkins;DRInormalizedGRFS38%;n=372);DRIGRFShazardinpublications
57%
36%
GRFSATIRPhaseII(n=23)
PTCy/BaltimoreDRInormalized*
(n=500)PTCy:resultsfromJohnsHopkins(Baltimore)and
Northside (Atlanta)
ATIR101:superiorOSvsliteratureforallogeneicHSCT(1yr)
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HigherOverallSurvival(OS)
Note:NOTbasedonrandomizedcontrolledtrials*Armandetal,Blood2014
9849HSCTpatients(CIBMTR2008-2010):• MRD,non-MRD,MUD,mismatched• PB,BM,cord• Leukaemia,lymphoma,MM,etc• Myeloablative,RIC
Conclusion:DiseaseRiskIndex(DRI)strongestprognosticfactor
61%55%
GRFSATIR101PhaseII(n=23)
AllogeneicHSCT*DRInormalized
(n=9848)
OverallSurvival(Armand2014)
0 6 12 18 24Monthsfromtransplantation
0
20
40
60
80
100
OverallSurvival(%
)
P<0.0001
ATIR101:superiorvsliteratureforPTCy (1yr)
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Note:NOTbasedonrandomizedcontrolledtrial*Ciurea2015(CIBMTRdata);Piemontese2017(EBMTdata),Salomon2012(Atlanta),Ciurea2012;Devillier2016;DiStasi2014;Esquirol2016;Sugita2015**Ciurea2015(CIBMTRdata);McCurdy2017(Baltimore),Devillier2016,Sugita2015(DRInormalizationbasedonArmand2014)
HigherSurvival(OS) ATIRPhaseII(007),n=23
PTCy/BaltimoreAtleast50%AML/ALL*(n=571)
LowerRelapse
9%
30%29%
22%
Relapse NonRelapseMortality
PTCy:resultsfromEBMT/CIBMTRdatabases,JohnsHopkins(Baltimore)andNorthside (Atlanta)
61% 60%57%
OverallSurvival
PTCy/BaltimoreNormalizedforDiseaseRiskIndex**n=158
0%
4%5%
24%
AcuteGVHDIII/IV
ChronicGVHD
LowerGVHD
OverallSurvival Relapse ChronicGVHD
CD34+stemcells(PhaseII)
9% 4%
αβ-T-cellDepleted(literature*)
40% 6%
PTCy(literature**) 29% 24%
Futuretrials:ATIR101asadjunctivetoαβ-TCDand/orPTCy
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+ATIR21%
+ATIR56%
+ATIR57%
…tofurtherimproveOverallSurvival…
…byloweringrelapse…
…withlikelylowimpactonGvHD
Futuretrial
*VerylimitedpublisheddataavailableforadultAML/ALL:EBMT2017poster,Preziosa etal**DRInormalizedCiurea2015(CIBMTRdata);McCurdy2017(JohnsHopkins),Devilier2016,Sugita2015
Futuretrial
Startwithhigherbaseline…
61%
Disease• Anemia duetodefectsinhaemoglobinandredbloodcells• Transfusiondependencyandironoverload,leadingtohighmortality
HSCT• Potentialcureofbloodformingsystem• ATIR201asadjunctivetoaαβ T-celldepletedhaploidenticalHSCT
Trialdesign• Pediatricpatientswithβ-thalassemia major• 10patients
Status• Centers:Regensburg,Tubingen,Manchester,Birmingham,London• TrialapprovedbyauthoritiesinUK&Germany
ATIR201PhaseI/IIinitiated:β-thalassemia
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ATIR:efficientcentralmanufacturing
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Efficientmanufacturingprocess:
5dayprocess;only2operatingdays
Nogeneticengineering
Disposablebags
Modestfacilityrequirements,no/lowcapex:
SimplecleanroomwithLAFcabinets,noviralvectors
OnesiteforUS/CanadaandEuropeeach
SignificantlylowerCOGSandmanufacturingfootprintthangeneticallyengineeredcelltherapyproducts
ATIR:easyfitintoroutinetransplantationcenterprocedures
Apheresis ShiptoKiadis
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Patient&donormaterial42hourholdtime(HypoThermosol)
Finalproductfrozeninliquidnitrogen(>12monthstability)
CentralKiadismanufacturing
Doseatbedside
Shiptohospital
14daysbeforeHSCTconditioning
28- 32daysafterHSCT
Routinelydoneforbonemarrowgraftsandproductsfrombloodbanks
5dayprocess
Annualpotentialfor(improved)haploidenticalHSCT
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1,200 2,000
4,200
8,300
8,400
-
2,000
4,000
6,000
8,000
10,000
12,000
14,000
16,000
18,000
20,000
US Europe
10,000
18,700*
Source:EBMT,CIBMTR,Passweg BMT2017,Besse JOnc Pract 2015,Lancet2015;*IfonlyEU:16,200**Calculationbasedon35%ofpatientsnotfindingamatcheddonor,onlyUSandEU
4,600
Currenthaploidentical
EligibleforHSCT,butnotyettreated**
CurrentMUD&cordblood
ATIRpatentprotection(owned/licensed)
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Seewordfile
Topic Family ClaimedPriorityDate LatestExpirydate
Devicewhichisusedfor photodynamictreatmentintheATIRprocess P014 July19,1996 June18,2017
MethodsoftreatmentforreducingorpreventingGVHDandapharmaceuticalcompositiontobeusedinthismethod
P015 October5,1999 October18,2021
Useoffragmentsorsupernatantfromphotodynamicallytreatedcells forpreparingvaccinesagainsthematologicaltumorsorfortreatinganimmunologicaldisorder
P016 December5,2003
December 2,2024(ifgranted)
Morerhodamine derivatives,theirsynsthesis anduse P019 April2,2001 January 28,2024
ImprovedphotodynamicprocessleadingtoATIRwithimprovedproperties P040 February19,
2015February19,2036(ifgranted)
Kiadiskeyexpectedmilestones
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SubmissiontoEMAofATIR101formarketingauthorizationapproval(done)Updatesonenrollmentandonopeningnewclinicalsites
2017
(Conditional)marketingauthorizationapprovalATIR101inEUInitiateATIR101asadjunctivetoPTCy and/orαβ T-celldepletedHSCTUpdatesonenrollmentandonopeningnewclinicalsites
2018
CommerciallaunchATIR101inEU(Interim)dataonthevariousclinicaltrialsforATIR101andATIR201
2019
Kiadis:neartermandlargeopportunityinHSCT
• Blockbusterpotential,targetpopulation28,700patients
• EUfilesubmitted,launchexpected2019(basedonPhaseII)
• PhaseIIIinitiatedforUSFDAapproval(superiorGRFStoPTCy)
• Upsidepotentialforsurvival(adjunctivetoαβTCDorPTCy)
• Efficientsupplychain
• Experiencednewteamwithbusinessandsupplychaincapabilities
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…sothatmanymorepatientswithotherwiseincurablediseaseswillhaveareasonablechanceoflongsurvivalandcure
Dr.E.Donnall ThomasestablishedbonemarrowtransplantationasatreatmentforleukemiaNobelLecture|1990
Additionalinformation
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ATIRproductcharacteristics
Clinicaltrialinformation(April2017)• CR-GVH-001• CR-AIR-007• CR-AIR-008
Other
ATIR101:alloreactiveT-cellsdepleted,potencyretained
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:Finalproductmanufacturedfromdonor:Cellsfromthedonor/startingmaterial
Typical example in CR-AIR-007
Proli
fera
tion
Inde
x (PI
)
Donor Recipient 3rd party CD3/281.0
1.2
1.4
1.6
468
10DonorATIR
Control:nodonorreactivity
Safety:depleted
allo-reactivity
Potency:otherreactivity
retained
FunctionalreleaseassaybasedonQualityTargetProductProfile&CriticalQualityAttributes
ATIR101:T-cellsreactiveagainstinfections&tumorretained
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Donor
ATIR Control
Myb628multimer
CD8T-cells
EBV CMV
CollaborationwithProf.AngelaKrackhardt,Medizinische Klinik III,Klinikum Rechts derIsar,TUMunich,Munich,Germany
ATIR101:T-cellsreactiveagainstEBVretained– examples
ExamplesoftwopatientsinclinicalstudywithATIR:
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EBVreactivationtriggeredresponseof(viralspecific)T-cellsinseveralpatients• IncreaseinCD3+T-cellsdetectedin
peripheralblood• EBVcopynumbersreducedafter
increaseinCD3+T-cells,indicatingeffectiveimmunologicalT-cellresponse.
PhaseICR-GVH-001:OverallSurvival(5year)
Patients:
19withadvancedhematologicalmalignancies(15notinremissionattransplant)
ATIR101doses:
10kcells/kgto5mln cells/kg;30daysafterHSCT
Results:
• 67%OverallSurvivalatmiddledoselevelafter5years
• NoacutegradeIII/IVGVHDrelatedtoATIR101atanydose
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OverallSurvival(OS)
DoseL1-L3
DoseL4-L6
DoseL7
0%
20%
40%
60%
80%
100%
0 6 12 18 24 30 36 42 48 54 60
TimeafterHSCT(months)
3patients;2,6-5Mcells/kg)
7patients,10-130kcells/kg
9patients,320k-2Mcells/kg
Note:un-manipulatedhaplo-identicalDonorLymphocyteInfusioncancausegradeIII/IVGVHDat50kcells/kg.
PhaseIICR-AIR-007:trialcharacteristics&endpoints
Design:open-label,singlearm,multi-center study
Patientpopulation:• AMLorALLinfirstremissionwithhigh-
riskfeaturesorinsecondorhigherremission
• Nosuitablematcheddonor• Haploidentical family
Locations:CA,BE,DE,UK(8sitesintotal)
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Primaryendpoint:• TransplantRelatedMortality(TRM)at6months
Secondaryendpoints:• AcuteandchronicGVHD• Immunereconstitution• Infections• TRM,relapse,OverallSurvival(OS)
Patientfollow-up(per28november 2016):• Median485days(range110– 742)
PhaseIICR-AIR-007:patient &donorcharacteristics
Patientanddonors• N=23patients(HSCT+ATIR101)• Medianpatientage(range):
41years(21-64)• Gender:13female,10male• Mediandonorage(range):33years(21- 61)
Diagnosis
AML:n=16(70%):• 11inCR1• 5inCR2
ALL:n=7(30%):• 4inCR1• 3inCR2
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Riskclassification
Cytogeneticriskprofile1:• Favorable 0• Intermediate 9(39%)• Adverse 14(61%)
Disease-riskindex2:• Lowriskindex 0• Intermediateriskindex 10(43%)• Highriskindex 13(57%)
1Mrozek K,etal.JCO2012,30(36):4515-45232ArmandP,etal.Blood2014,123(23):3664-3671
PhaseIICR-AIR-007:HSCTcharacteristics
Myeloablative conditioning
• TBI(1200cGy;n=11)ormelphalan(120mg/m2;n=12)
• Thiotepa (10mg/kg),fludarabine (30mg/m2
x5d)andATG(2.5mg/kgx4d)
HSCT
• CliniMACS® CD34isolationsystem(MiltenyiBiotec)
• Target:8-11x106 CD34+cells/kg,withmax.of3x104 CD3+cells/kg
Prophylaxis
• NoGVHDprophylaxis
• CMV/EBVmonitoring
• Prophylacticganciclovir/foscarnet (CMV+recipient/donor)
ATIR101infusion
• Day28postHSCT(median)
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PhaseIICR-AIR-007:causesofdeath(April2017)
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PeriodpostHSCT Classification No.ofpts Classificationofcauseofdeath
<6months
Relapse 1
TRM– Infections 2 AdenovirusandJCvirusinfections
TRM– Other 1 Pulmonaryembolism
6-12months
Relapse 1
TRM– Infections 3 Respiratory/pulmonaryinfections/distress
TRM– Other 1 Multi-organfailure
12-24months(ongoing**)
Relapse 2
TRM-Infections 3* Pneumonia/Sepsis/Septicshock
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*All3patientsimmunosuppressed,subsequentlycontractedinfections,leadingtodeath:2patientswhoreceivedun-manipulatedDLI’sandsubsequentlydevelopedsevereGVHD;1patientwithchronicGVHD**Onepatientstillinactivefollowup
Objective: Extendthelengthofprotection(furtherimproveTRM);investigateflexibilityforphysicians(insteadofun-manipulatedDLI)
Design: HSCTfollowedwithATIR101atday30,andadditionaldoseofATIR101atday72
Enrollment: 11outof15patientsenrolledandtreatedwithATIR101:5patientsreceivedonedoseofATIR101and6patientsreceivedtwodoses
Results:Confirmingsafety/efficacyfindingsin001/007withasingledose,notwithtwodoses- Singledose:nogradeIII/IVGVHD(median137daysfollowup)- Twodoses:gradeIII/IVGVHDinsomepatients
Continuation: Remaining4patientstobeenrolledandtreatedwithasingledose,accordingtoprotocol
PhaseIICR-AIR-008:studywithseconddose(April2017)
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Bellicum BPX-501:datainAML/ALL
Caspallo trial(Zhou2014)• 10pts• Pediatric,aged3-17• MostALL• CD34+HSCT• 3outof4patientstreatedwith
rimiducid totreatGVHDdiedfromrelapse(day57,158,552)
Otherpublicdatamostlynon-malignancies,children(GVHDlower)andmixCD34+andαβTCD
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ArthurLahr(April2017)ChiefExecutiveOfficer
• ChiefStrategyOfficerCrucell (NASDAQ/Euronext);headBD,M&AandM&SUS/EU
• BoardSanquin (Dutchbloodbank)• McKinsey&Co,Unilever
Robbert vanHeekerenChiefFinancialOfficer • HeadGlobalFinance&ControlOrganon
JanFeijen (April2017)ChiefOperationsOfficer
• Headoperations&supplychainJ&Jvaccines,Crucell andAvebe
• DevelopmentatGist-Brocades
Jeroen RoversChiefMedicalOfficer
• ChiefMedicalOfficerCeronco Biosciences• DirectorClinicalDevelopmentOrganon
MargotHoppeGeneralCounsel
• 20+yearsincorporatelegalaffairs,includingGist-BrocadesandDSM
Kiadismanagement:industryexperience,allfunctions
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