A BioPontis Alliance Report

Integrating Rare Disease Patients into Pre-Clinical Therapy Development;

Finding our Way with Patient Input

December 2016

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Integrating Rare Disease Patients into Pre-Clinical Therapy Development; Finding our Way with Patient Input

ABSTRACT Patientintegrationintodrugdevelopmentisbeingemphasizedbymanyregulatoryauthorities,patientorganizations,coalitionsandpharmaceuticalcompanies.However,thateffortrarelyifeverextendsintotheearliestdrugdiscoveryandpreclinicalphase,whentheactualtherapeuticstrategyisset.Theover7,000rarediseasesrepresentahugediversityofillnesseswithfrequentlypoorlyunderstoodclinicalpresentationandprogression.Therapeuticsdevelopmentinthisarenamustbeaddressedfarmoreefficiently,whichmeansthatpatientinputneedstoenterstrategydevelopmentattheverybeginningofdrugdiscovery.Inaddition,patientinvolvementshouldimprovethelaterexperienceinclinicaltrials,regulatoryreviewandcommercialdeliveryoftreatmenttopatients.

Thecurrenteffortwasdesignedtodefinemethodsandpracticesthatenabletheintegrationofpatientsintothedrugdiscoveryandpre-clinicalstagesofdevelopment.Wesawaclearneedtoengagefirstinadirectdialoguewithpatientorganizationleaderstolearnaboutwhatisimportanttopatientsandtoco-developpracticalmethodsforthisnewwayofworkingbetweenscientists,cliniciansandpatients.Theresultsoftwoworkshops,heldwithpatients’organizationswithintherareneurologicaldiseasecommunity,aredescribed.Theobjectiveoftheseinitialworkshopswastoinitiateanewpatientintegratedprocedurestartingintheearlieststagesoftherapeuticsdevelopment,tobetransferredtoproductdevelopmentcompaniesforthetransitiontoclinicaldevelopment,regulatoryapproval,anddistributiontopatients.

ThisprojectwassupportedbygenerousphilanthropiccontributionsfromShirePharmaceuticals,GlaxoSmithKline,TheBaillet-LatourFundandprivatedonorstoBioPontisAllianceforRareDiseases

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Integrating Rare Disease Patients into Pre-Clinical Therapy Development; Finding our Way with Patient Input

DavidSpencer1,BarbaraHandelin1,AllisonHarrigan2,FabianRiess2,JeanCampbell1,UrsulaDavis1,AnaMingorance1,RichardBasile1

1BioPontisAllianceforRareDiseases;2McKinsey&Co.Asignificantshiftisunderwayinhowregulators,pharmaceuticalcompaniesandresearchersareviewingtheroleofpatientsinthedesignandimplementationoftherapy(medicines)development.AsnotedbytheEuropeanPatientsAcademyonTherapeuticIntervention1:

“Thereisanindustry-widemovetowardspatientfocus,withthecreationofPatient-CenteredOutcomesResearchInstitute(PCORI)2,FDA’sPatient-FocusedDrugDevelopment(PFDD)initiative3,ClinicalTrialsTransformationInitiative(CTTI)4andthePatientFocusedMedicineDevelopment(PFMD)coalition5andothers.…Experiencetodatedemonstratesthatclosecooperationwithpatientshasresultedinincreasedtransparency,trustandmutualrespectbetweenthemandotherstakeholders.Itisacknowledgedthattheircontributiontothediscovery,developmentandevaluationofmedicinesenrichesthequalityoftheevidenceandopinionavailable.6

EMAandFDAhavehighlightedspecificobjectivesintheirguidancesandofficialpositionstatements;suchasbeginningthecollectionofnaturalhistorydataearlier,‘listeningcarefullytopatientsandorganizationsthatrepresentthemtolearnmoreabouthowtheyperceivebenefits,risks,andunmetneeds”7andto“moresystematicallyobtainthepatient’sperspectiveonadiseaseanditsimpactonpatients’dailylives,thetypesoftreatmentbenefitthatmattermosttopatients,andtheadequacyofavailabletherapiesforthedisease

Developmentoftherapiesforrarediseasesisincreasinglybecomingatestinggroundforbestpracticesinpatientengagementaswellasuseofsurrogatemarkers,biomarkersandflexibledesignofhumantrials.Thisisalldrivenbythespecialchallengesofworkinginnarrowlydefined(e.g.,byspecificgeneticmutation)patientpopulations8.Indeed,rarediseasepatientorganizationshavethemselvesledthe

1(http://www.patientsacademy.eu/index.php/en/file-download/eupati-reports/318-2014-07-23-eupati-po-i-meeting-case-reports/file)2http://www.pcori.org/about-us

3http://www.fda.gov/ForIndustry/UserFees/PrescriptionDrugUserFee/ucm326192.htm

4http://www.ctti-clinicaltrials.org/

5http://patientfocusedmedicine.org/

6AdaptedfromtheEMAframeworkhttp://www.ema.europa.eu/docs/en_GB/document_library/Other/2009/12/WC500018013.pdf

7Woodcock,J.,21st-CenturyCures:ModernizingClinicalTrialsandIncorporatingthePatientPerspective,,http://www.fda.gov/NewsEvents/Testimony/ucm404647.htm8RareDiseases:CommonIssuesinDrugDevelopmentGuidanceforIndustry,U.S.DepartmentofHealthandHumanServices,FoodandDrugAdministration,August201http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM458485.pdf

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initiationandadvancementofseveralrecentlyapproveddiseasemodifying,genotypespecifictherapies(CysticFibrosisFoundation,ParentProjectMuscularDystrophy).Evenso,theprimaryentrypointforpatientorcare-giverperspectiveshascontinuedtoremainatthetimeofrecruitmentforfirstclinicaltrials.Thisisdueinparttoafrequentlyarms-lengthrelationshipbetweencommercialdrugdevelopersandpatientsinthedrugdiscoveryandpreclinicaldevelopmentstage,whichisseenbycommercialdevelopersasapurelytechnicalphase.Theinclusionofnon-expertsinthescienceandclinicalaspectsofdrugdevelopmenthassimplynotbeenconsideredrelevanttosuccessespeciallyduringtheearly,morepurelytechnicalstages.

Intherarediseasefield,patientpopulationsaremoreknowledgeableabouttheirdiseasescomparedtomostcliniciansandscientistsbecausefewprofessionalshaveexposuretoenoughpatient’slifetimestoaccumulatedeepdiseaseknowledgeorexperience.Additionally,thelackofapatient-derivednaturalhistorydatasetbeforeinitiationofaproductdevelopmentcyclecangreatlyincreasetheriskoffailureinrarediseasetherapeuticsdevelopment.

ThenonprofitBioPontisAllianceforRareDiseasesisfocusedexclusivelyontheearlieststagesoftherapydevelopmentforrareneurologicaldiseases.Giventhebackgroundpresentedabove,wehavereasonedthatifpatientscanbemeaningfullyintegratedintotheearlieststagesofdrugdiscovery,e.g.,definingtherapeuticobjectives,identifyingrelevantsymptommeasurementsanddiseaseprogressionmarkersorthedevelopmentofrelevantoutcomemeasures,thiscouldgreatlyimprovethelikelihoodofachievingthetreatmentsthatpatientstrulyneedandwant.Inaddition,thisinvolvementcouldimprovethelaterexperienceinclinicaltrials,regulatoryreviewandaccesstotreatmentforpatients.Wethereforehavecommittedtodiscoveringpracticalmethods,practicesandtoolsforincorporatingpatientsdirectlyintoourpre-clinicaldevelopmentprograms.Ourproposaltointegratepatientsisnovelatthisearlypre-clinicaltranslationalstageoftreatmentdevelopment,andweseektoestablishpracticesthatcanbewidelyutilizedacrossallrarediseases–notjustforoneproductorraredisease.

Becauseweproposetobreaknewground,wewerefacedwithaclearneedtoengagefirstinadirectdialoguewithpatientorganizationleaderstolearnaboutwhatisimportanttopatientsandtoco-developpracticalmethodsforthisnewwayofworkingbetweenscientists,cliniciansandpatients.Toachievetheseobjectives,patientorganizationworkshopswereconductedin2016intheUSandEurope.

Thiswhitepaperdescribestheresultsofthefirsttwoworkshops,heldwithpatients’organizationswithintherareneurologicaldiseasecommunity.Twocriticalfactorsthatcanchangethedirectionandemphasisofthedevelopmentprogramwereexplored:thecreationofavisionforthenewtherapy(“targetprofile”)atthebeginningofthetherapeuticsdiscoveryeffortguideddirectlybypatientsintegratedformallyintothetherapydevelopmentteam,includingparticipationinassessmentoflikelyrisk/benefitandproposedendpointrelevancetodiseaseoutcomesatthepointwherealeadcandidatetherapyhasemergedandmustbeoptimizedforclinicaltrials.

MethodsanddesignofPatientIntegrationWorkshops(PIWs)

Eight(US)andnine(EU)representativesofrareneurologicalpatientorganizationswereinvitedtoparticipateineachoftwosingle-day-longPatientIntegrationWorkshops,oneheldinWashingtonD.C.onApril19andoneinLeuven,BelgiumonJune14,2016.

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Ourthanksgotothefollowingparticipatingorganizations.

Europe UnitedStatesAlternatingHemiplegiaFederationofEurope AssociationforFrontotemporalDegeneration

CMT-France BattenDiseaseSupportandResearchAssociationDravetSyndromeFoundation Ehlers-DanlosSyndromeSocietyC.A.R.E.S.

DystoniaEurope Erdheim-ChesterDiseaseGlobalAllianceEuropeanHuntingtonSociety FSHMuscularDystrophySociety

FriedrichAtaxieFördervereine.V. JainFoundationLigaMyastheniaGravis NBIADisordersAssociation

NBIA,TelethonItaliaandRareEpilepsy Sturge-WeberFoundationVSN–TheNetherlands

BeforeeachPIW,participantsweresentbackgroundinformationonthedrugdiscoveryanddevelopmentprocess.Ateachmeeting,thekeyaspectsofthisprocesswerereviewed(seeFigure1foranoverviewofthedevelopmentprocess).Threephasesofthedrugdiscoveryprocesswereidentifiedasbeingimportantpointsforpatientinputandparticipation;1)Theinitiationstepwhenthecharacteristicsofthedesiredtherapyaredefinedasobjectivesforthedrugdiscoveryprocess;2)therefinementstagewhenanimaltoxicityandoptimizationofthedrugmoleculeforabsorption,deliverytotheaffectedorgans,metabolism,etcareachieved;and3)thefinalstagewhenpreparationforanddefinitionoftheproposedhumantrialsisbeingdeveloped.

Figure1.Overviewofthedrugdiscoveryandpreclinicaldrugdevelopmentprocessasexemplifiedbysmallmoleculedrugtherapeutics.

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Thegroupwasalsointroducedtoanoverviewofthedifferenttypesoftherapeuticmoleculesortechnologiesthatcouldbechosentodevelopforanygivenraredisease(Figure2).Therationaleforwhichtechnologytochooseforaspecificdiseasetargetwasdiscussedwiththeimportantoutcomethatpatientrepresentativeshadnewappreciationforthemeritsandchallengesofwellestablisheddrugtypes(e.g.‘smallmolecules’orantibodies)versusnewertechnologiessuchasgenetherapy.Sincemanyrarediseasesarecausedbygeneticdefects,genetherapywasseenbymanyparticipantstobethemostdirectandeffectivetherapy.Assuch,thisdiscussionrevealedwashowimportantitwouldbeforpatientorganizationstoconsiderthemeritsofpursuingonlythishigherrisk,morecomplextherapyvsbalancingwithotherwellestablishedandlesscomplexchemicalcompounds(smallmolecules)orprotein(biologics)therapies.

Figure2.Overviewoftypesoftherapeutics

Followingthisintroduction,participantsdiscussedseveralexamplesofthetypesofinputstheymightbeaskedtogiveatvariousstagesofthedrugdiscoveryandpreclinicaldevelopmentprocess(Figure3).Thegroupalsocoveredwhattypesofactivitiespatientorganizationsalreadyundertakeandcouldexpandupontoinformthedevelopmentprocesssuchasregistries,tissuebanks,basicresearchsupportintotargetbiology,clinicalendpointdefinitions(includingpatient-reportedoutcomes)andhowtoachievebestpracticeswithinapatient/drugdevelopercollaborativeframework.

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Figure3.Examplesofpotentialpatientinputs.

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Aproposedpatient-orienteddrugdevelopmentprocess

1.TargetProductProfile

Patientrepresentativeandworkshopparticipantsagreedonthefollowingsetsofinputsthatpatientsanddrugdevelopmentscientistsshouldbringtothetableatthebeginningofararediseasedrugdiscoveryprogramandwhattheoutputofthatprocessshouldbe(Figure4).

Figure4.Patientandscientificinputstoasharedtargetproductprofileasabasisforrarediseasedrugdiscovery.

Drugdiscoveryanddevelopmentbeginswithassemblingthebiologicknowledgeaboutthedisease,andthemolecularpathwaysinvolved,todesignascientificplanofattackonthedisease;the“therapeuticrationale”.Shouldtheaberrantgenebesilenced,orshouldtheaberrantproteinfromthatgenebeantagonizedoralteredtobecomeeffectiveinsomeway,orshouldthebiochemicalpathwaythattheaberrantproteinparticipatesinbealteredatsomeotherpoint,alltocorrectthediseasepresentation?Giventhestrategy,whattechnologyshouldbeused?DecisionswillbemadeonwhethersmallmoleculedrugsorproteinbiologicsorRNAsilencingconstructs,genetherapyorcelltherapytechnologiesofferthegreatestchancesforsuccess.Basedonthestrategyandthetypeofdrugsought,assaysusingnormalanddiseasedtissuesoranimalmodelsofthediseasewillbecreatedtoseeiftherapycandidatescancorrectthedefect.Finally,thetherapeuticstrategyandknowledgeaboutthediseaseprocesswillbeusedtoproposeserumortissuebiomarkersaswellasclinicalendpointsthatcouldbereflectiveofthediseaseprocessorstageandthathopefullycouldbesensitivetotherapeuticeffects

Inordertocreateasharedtargetproductprofileforthedrugdiscoveryanddevelopmenteffort,patientorganizationsandthedrugdevelopmentteamwouldcombinetheirideasonallthesepointstocometoagreementontheprofileofthetherapytheyareseeking.Forexample,patientswillprovideinformationonwhatdiseasesymptomsaremostrelevanttotheirdailylivesandthedrugdevelopment

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teamwillrelatethatinformationtotheanimalmodelfeaturestheyproposetomeasureandtherelatedclinicalendpointsthatcouldlaterbestudied.Theycoulddeterminewhetherhaltingdiseaseprogressionissufficientorwhethershort-termsymptomimprovementandgainoffunctionisaminimumrequirement.Thepartiescoulddeterminewhatsortsofside-effectsmightbeexpectedfromthechosentherapeuticstrategyandwhichonesmightbetolerablelongtermandwhichmustbeavoidedsoasnottoworsenqualityoflifeevenmore.Theycouldalsosetdownwhichmethodsforadministeringthetherapy(oral,injectione.g.)arepracticalasopposedtoimpractical,giventheproposedbenefitlevelandthepatients’limitationstoadministermedications.

Patientorganizations,becauseoftheirknowledgeoftheirdiseaseandtheiradvocacywiththeirexpertclinicians,scientistsandphilanthropicdonors,arebestsuitedtobethedriversbehindthedevelopmentanduseofdiagnostic(oftengenetic)teststhathelpdefinethepatientpopulationthatcouldbenefitfromthedrugunderdevelopment.Fromthere,theycanassembleidentifiedpatientsontoorganizedpatientregistriesandworkwithclinicalspecialistsintheirdiseasetoinitiatelongitudinalnaturalhistorystudies.Thefunctionsofthosestudiesaretofullydescribethevarietyofclinicalpresentationsofpatientswiththediseaseandtodeterminehowthatpresentationprogressesovertime.Insodoing,theywilldiscoverwhichtypesofassessmentsaremostsensitiveandreliabletodiseaseprogressionandwillusethatknowledgeasabasisfordesigningbetterassessmentsthatcouldbeusedinclinicaltherapytrials(“clinicalendpoints”).Toadvancebiologicalknowledgeofthebasisoftheirdisease,patientorganizationscananddoworkwithinvestigatorstocreatetissuebankssothatresearchershaveaccesstorelevantsamplestostudyhowthediseaseaffectsspecificgenes,geneexpressionandbiochemicalpathways.

Theneedforwell-developedpatentprotectionwasraisedfromtheperspectiveofthefuturecommercializingcompany.Whilepatientorganizationswere/areawareofthis,itwasnotcleartomosthowtoensurethatthiseffortissafeguardedduringthediscoverystagesofresearchintheacademicinstitutionswheretheirgranteeresearchersareworking.Moreover,thepatientorganizationssoughtguidanceonwhetherorhowtosecurerightstothepatentsthatmaybefiledasaresultoftheirsponsorshipofresearch.Lookingforward,thegroupsagreedthatsomespecificguidancewasneededforthemonhowtoparticipateinmakingsurethatnewintellectualproperty(IP)iscreated,registeredandmanaged,sothatresearchmaterialsareavailabletoallresearchersinterestedinworkingonthedisease.

2.Leadoptimizationstage:assessmentofrisk-benefitprofileandproposedclinicalendpointrelevance.

Atthispointinthetherapydevelopmentprocess,candidateshavebeenfoundthatarenotonlypositiveinthescreeningassays,buthavealsobeenconfirmedtoexerttheireffectsinaccordancewiththeproposedtherapeuticrationale.Inaddition,theyappeartohavesufficientpotency,bioavailability,selectivityandsafetyforfurtherdevelopment,theeventualgoalbeinganapplicationforclinicaltrials(IND(USFDA)orCTA(EuropeanEMA)).Nowthatfarmoreisknownaboutthetherapyproperties,thetargetproductprofile,orvisionofthetherapy,canbeupdated.Moretargetedassessmentscanbemadespecificallyonwhetherthetherapyappearstobedoingsomethingusefulandwhetherornotthereistoohighasafetyorconveniencepriceforthatbenefit(Figure5).

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Figure5.Re-evaluationattheleadoptimizationstageofdrugdevelopmentofproposedtherapyrisk-benefitandpatient-relevantclinicalendpoints.

3.PreparationforClinicalTrials

Duringthisfinalphaseofpreclinicaldevelopment,thealignmentofthescientificandclinicalteamtotheintegrationofthepatientsshouldbeparticularlyclose.Someofthisalignmentwasobvioustobothscientistsandpatientrepresentatives,otherswererevelatory.Forexample,thedesignoftheearliestPhaseI/IIclinicaltrials,includingtheinclusionandexclusioncriteria,wasexpectedtobenefitfrompatientawarenessandinput.Bycontrast,whenpatientslearnedhowchallengingitcanbetodesignandimplementamanufacturingprocessthatcanbescaledfromresearchlabtohumandosingstudiestherewasimmediateappreciationforwhyavailabilityofproductcanlimitandstalltrials;understandingthiscouldleadtopatienceandsupportforproblemsthatmightariselater.

Referringbacktotheearlierstagesoftheprocesswhentheexpansionorinitiationofregistrieswouldbeconductedbypatientorganizations,theworkshopparticipantscouldeasilyseehowvaluablethisproactiveapproachwouldbeatthefinalstagewhentheplanforinitiatingclinicaltrialsisunderway.Moreover,patientscouldreadilyseehowtheirparticipationinthedevelopmentteamwouldprovidethemwithamoreindepthunderstandingofthetherapythatwillnowbeofferedtopatientsintheproposedclinicaltrial.Patientsreflectedhowmucheasieritwouldbetoeducatetheircommunitiesontheparticularsofthedrugandthetrial,havingbeenpartoftheprocessforboth.

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SpecificPointsofConsensus

Thefollowingpointsemergedfromthediscussionsduringtheworkshops.

1. Jointworkbetweenpatientorganizations,investigatorsandpharmaceuticalcompaniesisnecessaryforthecreationanduseoftissuebankstosupportbiomarkerdevelopment.Tissuefromthesebanksneedstobeavailabletoallresearchers,whichhasfrequentlynotbeenthecaseinthepast.

2. Therewasconsensusthatlongitudinalstudiesarecrucialingainingaclearerunderstandingoftherangeofclinicalpresentationsinthepatientpopulation,assessingdiseaseprogressionandinsettingupbetterclinicalendpointsforclinicaltrialsoftherapeutics.Suchstudiesbenefitgreatlybycollaborationbetweenpatientorganizations,clinicians,biomarkerresearchersandpotentialdrugdevelopers.

a. Biomarkersandsurrogateendpointscanstronglysupportorindeeddrivepivotaltrialsbutneedtobeidentifiedinearlydevelopmentandsupportedbybiobankresourcesmoreopenly.

b. Patientnarrativescanaddstronglytoendpointdevelopmentbutareproblematica)forinclusioninregistriesandb)withregardtocontinuousdatasubmissionovertime(withoutbeingburdensometopatients).

3. Developmentoftargetprofilesfordrugdiscoveryandnovelendpointscouldbekeyareasofinteractionbetweendrugdevelopersandpatientgroups.

4. Patientorganizationsstruggletomaintainfocusoftheireffortsalonganorganizedpathtotherapeuticdevelopmentandtounderstandwhattheprerequisitesareateachstep.Itwouldbevaluableforpatientorganizationstohaveadevelopmentreadinessinventorytool.Thistoolwouldallowpatientorganizationboardstotargetfundsmoreeffectivelyandpatientorganizationstoorganizeandexecutetheirresearchmeetingsbetter.Immediatelyaftertheworkshops,theauthorsworkedwithpatientorganizationrepresentativestodraftandpilotthetool.

5. Patientorganizationswouldliketocollaborateonatemplateforcontractscoveringownershipandaccesstointellectualproperty(IP),animalmodelsandcelllinessothataccessandIPsecurityareassured.PatientorganizationsweresupportivethatthedrugdevelopersowntheIPinjointprojectsinamodelwherethefinancialbenefitscanbesharedwithallparticipantsasprojectsmature.

6. DrugdevelopersneedpatientinputtoadvanceanewtherapeutictotheINDstage,butpatientwillingnesstoshareinformationvariesbydisease.Patientgroupscouldshowpatientshowimportantthedatacanbebysharingacaseinwhichpatientinputdrovesuccessindevelopment.

7. Thereisnoformalmechanisminplaceforpatientorganizationstohelptheirmemberpatientsassessrisk-benefitaspectsofnewtherapeuticsbeforeenteringaclinicaltrial.Therewassupportfortheideaofdevelopingalistofquestionsforpatientstoconsiderandeducationalmaterialsonwhattoexpectinatrialbeforeparticipatinginatrial.

a. Thatwouldnotonlypotentiallyimproverecruitmentbutalsopatientretentioninongoingstudies.

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b. Inordertodothiseffectively,patientorganizationsneedtheirpartners(pharmaceuticalcompanies)todisclosemoreinformationaboutthetherapeutic,thedevelopmentplanandpotentialrisks.

c. Riskappetiteofpatientsishighlydependentonthepatient’scurrentqualityoflifeandthepredictedlevelofefficacyofthenewtherapeutic.

8. Therewasconsensusthatanumberoflessonscanbelearnedfromrecentexamplesoforphandrugapprovaldiscussions.Theystronglysupportthecontentionthatcompaniesmustworkevenmorecloselywithpatientorganizations.Relyingontheorganization’sunderstandingofthedisease,adrugdeveloperisinabetterpositiontodefineendpointsandinclusioncriteriaforclinicaltrials.

BackgroundoftheInitiative:BioPontisAllianceforRareDiseases

BioPontisAllianceforRareDiseasesisdedicatedtothe350millionchildrenandadultslivinginshadowaroundtheworld,afflictedwithdevastatingdiseasestooraretobenoticed.Geneticcausesareknownformanyandtechnologytocreatetreatmentsisavailable,yetonly5%haveanytreatment.Academicresearchersfindcausesbutcannotgeneratemedicines.Pharmaceuticaldevelopersfrequentlycannotjustifyrisky,early-stageinvestmentforsuchsmallpopulations.Patientorganizationswantprogressbutlackexpertise.BioPontishasdesignedanovel‘ProductivityAlliance’modelthatunitesthesecommunitiesintoanefficientsystemforparalleldevelopmentofmanytherapies.

Importantly,ultimatesuccessinbringingtreatmentstopatientsreliesonthepharmaceuticalindustrydoingtheirparttoconductclinicaltrialsandmakedrugsavailabletopatients.ThemissionofBioPontisAllianceistobridgethegapbetweenresearchresultsandpotentialtherapiesbygeneratingasteadyflowofwelldesigned,developedandvettedcandidates.

Thedevelopmentofeffectivetreatmentscanbevastlyimprovedbyintegratingpatientsmeaningfullyintotheearlieststagesofdefiningtherapeuticobjectivesandrelevantoutcomes.Thisinvolvementshouldimprovelaterexperienceinclinicaltrials,regulatoryreviewanddeliveryoftreatmenttopatients.Gettingtheseandotherfactorsmorecloselyaligned,incollaborationbetweendrugdevelopersandpatientswiththetargeteddisease,andwithclinicalandbasicscienceresearchers,webelieveshouldhelptotargetthemostmeaningfulhealthoutcomeimprovementsandavoidmistakeswithclinicaltrialdesign(e.g.,endpoints,biomarkers,andinclusion/exclusioncriteria)astreatmentsenterhumanclinicaltrialstudies.

Theworkshopsandtheiroutputarethebeginningofanewblueprintthatweareco-creatingwiththecommunityofpatientorganizations.Theconceptsandconsensusonpracticalmethodsforintegratingpatientsintodrugdiscoveryandpreclinicaldevelopmentwillnextbeimplementedinspecificdrugdiscoveryprogramsduring2017,inparallelwithfurtherexplorationofadditionalimprovements.Movingforward,theinterestsofregulatorsandfuturecommercialpartnerswhowillbringcandidatemedicinesthroughclinicaltrialsandtothepatientswillalsobeexploredinfutureconferences.Thegoalistoestablishanewpatientintegratedcontinuumstartinginpreclinicaldevelopmentthentransferredtoproductdevelopmentcompaniesforthetransitiontoclinicaldevelopment,regulatoryapproval,anddistributiontopatients.