Partners forLifeAdvancing tomorrow’smedicines.

FujifilmDiosynth BiotechnologiesTexas

ContractDevelopmentandManufacturingOrganization

2

GlobalVisionTobetheleadingandmosttrustedglobal

ContractDevelopmentandManufacturingOrganizationpartnerin

thebiopharmaceuticalindustry.

One Global Company

3SITES

Billingham,UKCollegeStation,TXRTP,NorthCarolina

~1,200EMPLOYEESWorld Wide6

LICENSESForcommercialmanufacturing

25+YEARS

OfBiologicsCDMOexperience.

300+MOLECULES

Inprocessdevelopmentand/ormanufacturing

Whatweoffer

RegulatoryApproval LaunchPhase IIIPhase I Phase IIPreclinical

GeneExpression&Strain/CellLineDevelopment

ProcessInvention

Pre-ClinicalManufacture

ProcessDevelopment&Optimization

Analytical&Stability

cGMP Manufacture

Fill/Finish(ViralProducts)

ProcessCharacterization

ProcessValidation

LatePhasecGMPManufacture

Stability

CommercialProduction

Post-approvalActivities

Stronginspectionhistorybythemajorregulatoryagencies

FDBTManufacturingFacilities,CollegeStation,Texas

NationalCenterforTherapeuticManufacturing- 152,000ft2‒ FlexiblemultiproductearlystagecGMP‒ MobileCleanRooms‒ WorkForceTraininglabs

TexasBiomanufacturingFacility(TBF-100)– 117,000ft2‒ Flexiblemultiproductmodifiedopenballroom‒ 2x2000LSingleusecellbasedmanufacturingtrainsinstalled‒ Capacityfor10additionaltrains

FlexibleBiomanufactuirngFacility(FBF-200)– 76,000ft2‒ Simultaneous,multiproductviralprocessmanufacturing

facility‒ Designedforlatestagecommercialmanufacturing‒ MobileCleanRoomTechnologyoperatingatBSL2+,BSL3

capable.

FinalDrugProductCapacity‒ InstalledandqualifiedbyQ42018

PrivateandConfidential

FDBTProcessDevelopmentLab

• 7000ft2ofBSL-2laboratoryspace• SingleuseMicroBioreactorsupto200LSingleUseBioreactorsforsuspensioncultures

• CellStacks,Hyperstacks,andICellis foradherentcultures• Fullpurificationandanalyticaldevelopmentsupport

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PrivateandConfidential

OverviewofFDBTPDDepartment

• Department– 24Scientistsgrowingto30byyearend– VirologyandAnalyticalDevelopment– UpstreamProcessDevelopment– DownstreamProcessDevelopment

• DepartmentGoal– Closed,continuous,singleuse-basedprocessing,usingstandardizedapproach

– Strongfocusonlatesttechnologyandinnovation

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PrivateandConfidential

VirusExpertiseandCellCultureSkills

• ExecutedAdenovirus,AAV,InfluenzaandBaculovirusprograms

• Additionalexpertisein– Flaviviruses,Rotavirus,Lentivirus,retrovirus,CMV,Poxvirus,HSVandHepA

andB

• Suspensiontoadherent:Expi293F,A549• Adherenttosuspension:Vero,HEK293• SuspensionCelllines:HEK293,A549,SF9,EB66andDaudi• Adherent:MDCK,Vero,HEK293• AdaptedCellstoSera-freegrowth:Vero,MDCK,HEK293

PrivateandConfidential

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VirusQuantitationMethods

• PlaqueTiter• TCID50

• InfectiousCenterImmunostaining• HAtiter• DualcolorFlowCytometrytiterassays

thatcanshowbothvirusandinsert• Totalviralparticles

– NanoSight– A260– HPLC

• Genomecopynumber(RT)qPCR

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PrivateandConfidential

AnalyticalCapabilities

• HPLC- Agilent1260UHPLC,Agilent1200HPLC- HitachiChromaster HPLC- ThermoDionex UltiMate 3000UHPLC

• HostCellDNA• CE/SDS-PAGE/WesternBlot• ELISA• PCR/qPCR/dd PCR• RestrictionAnalysis

PrivateandConfidential

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• DoE,Screening,DesignSpace• Parallelcellculture• ContinuousImprovement• Troubleshooting

Small-ScaleModels:QualitybyDesign

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PrivateandConfidential

Scale-UpandScale-Down

SingleuseMicroBioreactors

ScreeningMedia,DO,pH,etc(noKLa)

1/1000scale– reducecosts;increasecapacity;

DASGIPParallelBioreactor± HF(1/200)

SUBsfromPilot-ScaleBioreactor± HForATF(Confirmationruns,TechTransfer,Demonstration,

Engineering)toManufacturing

Processdevelopment;ContinuousImprovement;Troubleshooting;

PrivateandConfidential

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GMPEquivalentProcessPilot-Scale

• 1x10LBioreactorw/ATF2• 1x50LBioreactor± ATF6– Perfusion– HighCellDensity

• PerformedinMCRorPDlab

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PrivateandConfidential

Adherent2Dvs FixedBed3DCulture

1xHS36=1E10cellsà 100xHS36=~1E12cellsSeeding@1E5/cm2

Seeding@3.2E3/cm211dayculture=2.3E5/cm2=~1.5E12cells

Seeding@3.2E3/cm2à ~1E10cells

PrivateandConfidential 15

PrivateandConfidential

• Chromatography– 1xAKTAExplorer,2xӒKTAAvant,3 xӒKTAPure,3 xӒKTAPilot,– Columnbase:BPG,HiScale,XK,INdex,OmniFit,

• CellLysis– 1xPandaPLUS homogenizer

• Filtrationandclarification– 1xSpectrumKrosflo,1xAKTAFluxS,3xBeckmanAvanti(laband

demoscale),CustomsingleuseTFF(labscaleanddemo),MilliporeMillistakdepthfiltersystem.

• Mixersystems– PallAllegroMixtanks,LevMixandMagMixsystems

• In-processanalytics– SDS-PAGE,HPLC,Nanosight,qPCR,ELISA

KeyBioprocessDSPEquipment

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PrivateandConfidential

• Attheendofdevelopmentalabscaledemonstrationrunisperformed• Allparametersdirectlyscaletomanufacturingscalewithsametimings• ProcesstransferredtomanufacturingbyProcessSciencesandPD• PDprovide‘ontheground’forengineeringrunandprovidedtechnicalsupportforthe

fullmanufacturingcampaign

Demonstration&MFG-ScaleOperations

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PrivateandConfidential

Summary

• AvailableGMPmanufacturecapacitytoproduceclinicalI-IIImaterialsandcommercialproductsFlexiblefacilitieswithmobilecleanroomdesignSingleuseupstreamanddownstreamprocess

• DeepunderstandingofviralproductsandprocessesVirologyexpertWellestablishedprocessdevelopmentteamswithstrongtrackrecordwithinFDBnetwork

• RegulatoryknowledgeandcommercialmanufactureexperienceAnintegratedglobalqualityorganizationConducted>24 ProcessCharacterizationprojectsandcompleted>10ProcessPerformanceQualification(PPQ)CampaignswithinFDBnetwork

FDBThasasolidfoundationandanintegratedtechnicalandregulatorynetworktoassurethesuccessofGMPmanufactureforclients

PrivateandConfidential

• FDBTthanksCPRITforsupportwiththesetuptheProcessDevelopmentLaboratoryinCollegeStation.

Acknowledgements

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Partners forLifeAdvancing tomorrow’smedicines.