Innovative Medicines Initiative

www.efpia.eu

EMA-EBERegulatoryConferenceonATMPs Salah-Dine Chibout, Novartis

Global Head Discovery & Investigative Safety/ Global Head Preclinical Safety Therapeutic Areas

2www.efpia.eu

Mul-plecompaniesjoinforcewheretheywouldfailalone:Iden&fymissingorweaklinksinmedicinespathwaysthatholdprogress

Combine(o:en)proprietaryknowledge,dataandassetsOpenthemupforchallengebyandcollabora-onwithpublicpartnersValidateproposedsolu&onsduringprojectlife&meinR&Dprac&ce

Solu-onsfordiseaseswithhighburdenandcostforpa-entsandsociety

Solu-onsthatchallengecurrentbusinessmodelsandfocusonvalueforpa-entsandsustainablehealthcare

Trackingandaddressingsciencegapsandinefficienciesfromdiscoverytodiseasemanagement

IMIacceleratesinnova-on

3www.efpia.eu

  Publicprivatepartnership  Companiesandpublicpartnersworktogether  Industrycostisnotreimbursed:itisourinkindcontribu&on  Publicpartners(includingcompaniesupto€500mioturnover)

costisreimbursedbyEU:grantsforcollabora&ngwithindustry

  Industrydefinestheresearchagendaandprojects(butdoesnotchosewithwhomtowork)  Beyondthepublica&on:impactonresearch,regulatoryand

medicalprac&ce

  Managedbyaneutralbrokerthatallowspar&cipa&onofauthori&esandpa&ents

Essen-alfeaturesforresearchandpolicyagendas

4www.efpia.eu

TheInnova-veMedicinesIni-a-ve:thelargestpublic-privatepartnershipfor

healthresearchworldwide€5,276billion

IMI1€2billionfrom2008–2014IMI2€3,276billionfrom2014-2024

PartoftheEUFP7andHorizon2020R&Dfunding

Source:hUp://www.imi.europa.eu/content/mission

5 www.efpia.eu

EFPIA direct and indirect members

3.

1. 2.

What are the results ?

= in IMI2 consortia

1,638

3,276

From H2020

2014 - 2024

1,638 Billion € 1,638 Billion €

3,276 Billion €

+

1,425

Private Partners

Public Partners

CASH for grants for PUBLIC PARTNERS

Other sectors213

People

Consumables

Cash

Laboratories

Cash

Improve R&D

Improve outcomes & safety

Speed up patient access

The publiccontribution

The privateIndustry in-kind contribution

Distribution of IMI funding per area

Infectious diseases

Drug discovery

Brain disorders

Metabolic disorders Drug safety

Stem cells

Cancer

Data management

Inflamatory disorders

Biologicals

Geriatrics

Lung diseases

Education & training

Sustainable chemistry

Drug delivery

Drug kinetics Relative effectiveness

7www.efpia.eu

8www.efpia.eu

End-to-End:Alzheimer’sExample

Ae-onomyInterven&ons

andModelling

EMIF-ADCharacterisa&

onandModelling

Pharma-CogBiomarkers

EPADTrialandModelling

ROADMAPOutcomesdefini&on

andtracking

LegalandEthicalframework,Parent

cohorts,fingerprin&ng,databrowser

Trial,Hypothesisvalida&on

Knowlegebase,novelhypothesesandbiomarkersPa&entaccess,

healthcaresystems

Combina&onoftoolstoaccuratelymeasuredisease

progression

9www.efpia.eu

End-to-End:R&Daccelerator

Targetvalida&on

ELF

HittoLead

Enable

Biomarkeraccelera&on

SAFE-T

BigData

EMIFEHR4CR

ClinicaltrialsNetworks

EU-AIMSCOMBACTE

10www.efpia.eu

EuropeanLeadFactory

Ra-onaleNeed

1. Accesstohigh-qualitychemicallibraryforacademics/SMEstotranslateacademicbiologicaldiscoveries/targetsintosuitablechemicalmaUer

2.  Accesstootherwiseuna`ainablechemicalspaceforpharmapartnersthroughcompoundsharingandsynthesisofnovelchemicallibraries

3.  Accessnewbiologyfromacademia/biotech

Aim

•  Providestar-ngpointsforleaddiscoveryorhigh-qualitypharmacologicaltoolsbothforacademics/SMEsproposingtargetsandEFPIAcompanies.

•  Createpartneringopportuni-esforpublicpartnersandEFPIAcompaniestoprogresshitsalongthepharmavaluechain

IMI funding: € 80 Mio Academia / Biotech cont. € 25 Mio Pharma resources : € 91 Mio TOTAL PROJECT COST: € 196 Mio Duration: 01.01.2013 – 31.12.2017

Funds

PartnershipProjectProfileShareBurdenand

Risk

Standardiza&onandRegulatoryBodyInterac&on

Collabora&onIndispensable

DirectPipelineImpact

MethodsandTools

11www.efpia.eu

Boos-ngDrugDiscoveryEuropeanLeadFactory

SevenPharmacompaniesprovidedahigh-qualitycross-sec&onoftheirin-houselibraries

JointEuropeanCompoundLibrary

EuropeanScreeningCentre

DRUGTARGETS

LIBRARYDESIGNS

EFPIAcontribu-on(>300,000cpds)

Publiccontribu-on(200,000cpdsby2017)

50%EFPIAtargets50%publictargets

Publictargetsthroughcrowd-sourcingprocess

Chemistryconsor&umdesignsandsynthesizedPublicCompoundCollec&on(PCC)

Totalbudget:

€196million

12www.efpia.eu

Shortandlong-termbenefitsEuropeanLeadFactory

13www.efpia.eu

EuropeanLeadFactoryWhat’sinitforthestakeholders?

Output

Progress Public programme advanced to be developed within IMI‘s programme; a further project lead progressed as asset in ScandiCure start-up

Knowledge Training and education activities increased public knowledge on early drug discovery; establishment of a network of scientists working in drug discovery across Europe; more than 40 publication in peer-reviewed journals

Public target proposals 129 Accepted

targets 73 Public screens completed 49 Qualified hit

lists (QHLs) 43 Improved hit lists (IHLs) 12

Capabilities Access to a unique, unprecedented screening library, assay development, and state-of-the-art screening including hit validation capabilities ü

2/3 from academia 1/3 from SMEs

14www.efpia.eu

Goal: Support the evolution towards outcomes-focused and sustainable healthcare systems, exploiting the opportunities offered by big and deep data sources

TheBigDataforBe`erOutcomesprogramme

Design sets of standard outcomes

and demonstrate value

Increase access to high quality outcomes data

Use data to improve value of HC

delivery

Increase patient engagement through

digital solutions

COORDINATION AND SUPPORT ACTION (CSA)

HEMATOLOGIC MALIGNANCIES

PROSTATE CANCER

CARDIOVASCULAR

1 2 3 4

MULTI-DISEASE / MULTI-MORBID PATIENTS

DISTRIBUTED DATA NETWORK

ROADS: ALZHEIMER'S DISEASE

Coordination and operational topics

Themes / Enablers

Disease- specific topics

15www.efpia.eu

HARMONYprojectToimproveoutcomesinHematologicMalignancies,

weareteamingwithleadingins&tu&onsacrossEurope

HealthcareAllianceforResourcefulMedicinesOffensiveagainstNeoplasmsinHematologY

Pharma Regulators/HTAs

Medicalassocia-ons

Universi-es

Researchinst.andhospitals

Pa-entassocia-ons

Techandbiotech

LargestfundedprojectwithinIMI251partners,including44publicpartnersfrom10differentEUcountries

"IMIprojectsarebestpracJceintheindustry"–FDArepresentaJve

16www.efpia.eu

  Based on feedback from the IMI Stakeholder Forum on AdvancedTherapies,fivepoten-alIMI2topicsarecurrentlybeingconsidered:

  PrecisionGenomeEdi-ng(PGE)

  Clinicaldevelopmentandpa-entaccess

  Clinicaldevelopmentofcelltherapiesincancer

  Manufacturing

  Immunogenicity

ATMPsKeychallengesandfutureIMI2topics

PrioriJsedfordevelopmentin2017

17www.efpia.eu

  Scope  Addressgapsinourunderstandingofprecisiongenomeedi&ng

(PGE)biology,func&onandapplicability.  Increaseconfidenceintheaccuracy,safetyandefficacyofthe

technologiesforbothresearchandtherapeu&capplica&ons.  Examplesofdeliverables

  Novelcharacteriza&onassaysandtoolsforthequan&fica&onofon-target/off-targeteffects,ie.NewDNAanaly&ctechnologiesoradvanced‘nextgenera&onsequencing’(NGS)plahorms. Op&miza&onofexis&ngPGEplahorms-ie.Bioinforma&ctoolsanddesignguidelinestoincreasetargetselec&vity.  Developmentofnewpre-clinicalcell/animaltes&ngparadigms,ie:  Developandprovideaccesstoqualifiedreagents,plahormsanddata.  Definetheboundariesbetweenthecompe&&veandprecompe&&vespace,throughcon&nueddialoguebetweenresearchers,manufacturersandplahormdevelopment,throughouttheprogramme.

PrecisionGenomeEdi-ng(PGE)

18www.efpia.eu

  Scope  Frameworkforthedata-enabledop&miza&onofclinicaltrialsfordifferenttypesofATMPs.  Infrastructureandmethodologiesfortheefficientu&liza&onofexis&ngandnewregistriesandotherdatarepositories.  Enhanceinteroperabilitybetweendatabasesandintegra&onofdata Updatepolicies,processesandqualifica&onpathwaystoassessclinicalu&lityofexis&ngdataandnewevidencerequirements.

  Examplesofdeliverables  Technicalcapabili&esarounddatasourcestandardsandinteroperability.  Qualitystandards,accuracyandregularityofdataentry,repor&ngandanaly&cs.  Developnewdatanetworkarchitecturesandlinks,aswellasdatasetqueryprotocoldesigns,toavoidfragmenta&on.  Increasebuiltinflexibilitytoaccommodateemergingknowledgeandchangingrequirements.  Addresschallengesindatabasesustainability  Clarifystatusofpa&entleveldataprotec&on,accesscontrolsandsurveillance.  ClinicaltrialregistriescouldalsoexpandtoprovideevidenceinfurthersupportofHTAevalua&ons,focusedonpa&entoutcomes.

Clinicaldevelopment

19www.efpia.eu

  Scope  Capturethechallengesacrossthepathwayfromthebenchtothebedside,andacrossthedifferenttypesofATMPs.  Clarifyevidencerequirementsforacomprehensiveassessmentandcommercializa&onframework.  Allowsufficientflexibilitytoaccommodatethepaceofscien&ficprogress.  Securetheappropriateuseofhospitalexemp&onandleverageexis&ngschemes,ie.Orphan/rarediseasefunds.

 Examplesofdeliverables  Analysisofpipelineprojectsandcommercialproducts,investmentdecisionsetc.  Iden&fysuccess/failuredriversandkeygo/no-godecisionfactorsacrosstheproductjourneyfromR&Dtothehealthsystems(casestudies).  Deviseanaly&calframeworksandperformanceindicatorstocompareEUcountries,withUSandotherglobalcompe&tors.  Model/proposenovelreimbursementandpaymentschemes.  TabulatethekeyHTAconsidera&onsandcontrastwithevidenceforregulatoryapprovalsandsurveillance.  Analyzecaseexamplesonhospitalexemp&onacrossMemberStates.  Iden&fyandevaluateexis&ngandproposenewmodellingmethodsanddatatools(ie.Registries)throughspecificprojectsandworkstreams.

Pa-entaccess

20www.efpia.eu

  Scope  Addressgapsinearlyfinancingofproof-of-conceptstudies.  Improvecomparabilityofclinicalbenefitofcelltherapiesincancer.  Enablecombina&ontherapywithcheckpointinhibitorsandtargeted

therapies  Examplesofdeliverables

  Public-privatepartnershipinpre-PoCstagetoimprovenumberandqualityofclinicallytestedapproaches  Earlyfocusondemonstra&ngclinicalbenefit–aloneorincombina&onwithcheckpointinhibitorsandtargetedtherapies-ofcellulartherapies  Searchforbiomarkersofac&vityandmodeofac&onofcelltherapies.  Defineandstandardizeproduc&onqualitystandards&specifica&ons.  Analysefeasibilityofproduc&ononanadequatescale  Focusinves&gatorson„affordabilityandprofitability“.  Useofhistoricalandreal-worldevidencetocompareoutcomesinATMPclinicaltrials.  Definetheboundariesbetweenthecompe&&veandprecompe&&vespace

Howanoverarchingprojectcouldlooklike:ClinicalDevelopmentofCellTherapiesinCancer

21www.efpia.eu

  Scope  Technologicalinnova&onincelltherapyandgenetherapyproduc&on,

withspecificaUen&ontoclosedsystems,automa&onandmonitoringtechnologies

  Par&cularemphasisontherapeu&cscaleproduc&onandGMPstandardsatreasonablecost,achievingregulatorycompliance.

  Deliverables  Twomaintypesofautoma&onprocessesshouldbedevelopedinorderto

addressbothcondi&onsofop&malcellgrowth,namelyforadherentcellsinflasksandforcellsinsuspensionorsemi-suspensioninbioreactors.Robo&sedtechnologiesandcontrolledmethodologiesforcGMPbankingofcelltherapyproducts.Large-scalebankingofclinical-gradecelltherapyend-productsrequiresincreasingappropriatelyallsafetymeasuresanddesigningfullycontrolledproceduresbothforfreezingandthawing.

  Addressingtheques&onofahugediversityofcellandgenetherapyproducts.

  QualitycontrolsandstandardsusingtheproceduresofQualitybyDesignandQualityRiskManagement(ICHparadigmusedforchemicalcompoundsproduc&on)

  Rulesforcon&nuedengagementbetweenscien&sts/manufacturersandregulatorsbasedonriskassessmentalongtheprogramme

ATMPManufacturing

22www.efpia.eu

  Scope  Immunogenicityofdifferenttypesofallogeneiccellsources.  Impactofthediseaseontheimmuneresponses.  Impactoftherouteandscheduleofcelladministra&on.  Clinicalinves&ga&onofimmuneresponsesandtheirimpactonsafetyand

efficacyoftheATMP.  Deliverables

  Understandingtheinnateandadap&veimmuneresponsesagainstdifferentallogeneiccelltypes.

  Insightintheintensity,specificity,kine&cs,andpersistenceofsuchimmuneresponses.

  Dynamicsofmemoryresponsesuponrepeatedadministra&on.  Understandingtheinfluenceofgivenpathologiesonthean&-cellimmune

responses.  Clinicalassessmentoftheassociatedsafetyaspects.  ClinicalassessmentoftheimpactofimmuneresponsesonATMPefficacy.  KnowledgeoftheimpactofHLAmatchingandmismatchingonsafety/

efficacy.

Immunogenicity

23www.efpia.eu

  IMIisdelivering

  This is a truepartnership,where companies, publicpartnersandSMEsworktogether

  There is an opportunity to transform the ATMPlandscape

Conclusion