Niamh Kinsella, Paul Chamberlain, Josefin-Beate Holz, Paula Salmikangas and Jenny Sims from the Early Development Group at NDA Group
Maximising Value in Early Development
The Goal
Conclusion
The Challenges
• Defininganearlydevelopmentstrategyandimplementingitintoan overallstrategicroadmapisaveryvaluablecomponentofoverall productdevelopment• Theroadmapprovidesthescientificandcommercialpullandregulatory pushtosuccessfullynavigatetowardsproductapproval• Theendpointisthemaximisedcommercialvalueforapotentialdrug producttoapartner,licensororacquirer.Thisinturnmaximisesthe corporatevaluethroughtheachievementsofvalueinflectionmilestonesand providespotentialforcorporatefinancingandexitstrategies
Selecting product candidates with the highest probability of success and applying rigorous risk-based management in development maximises the value of biopharmaceutical products and increases speed to the clinic and registration.
• Biotechcompaniesoftendeveloptheirleadassetstoastagewherepartnering becomesfeasible• Acriticalgoalistoaddasmuchvalueaspossibleduringearlydevelopmenttomaximize thelikelihoodofsuccessfuldealwithcorporatepartnerand/orachievingalternativeexit opportunitiesforthecompany• TheBiotechcompanywillfocusonspeedandqualityintotheclinic• Thecorporatepartner/investorisinterestedtoenrichtheirportfolio,butalsotoachieve commercialsuccess(requiringregistrationoftheproductinkeymarkets)• Criticalactivities,milestonesanddecisionpointsaswellasriskmanagementtoolsthat supporttheefficientadvancementofaproducttowardsregulatoryapprovaland commercializationneedtobemappedoutataveryearlystage–oftenstartingpriorto identificationofaleadcandidate
Focuses on defining input data to inform decision-making at critical stages:• Prioritisesresourceallocationonactivitiesmostlikelytoaddcommercialvalue whileminimisingregulatoryrisk• Stratifiesincrementalinvestmentinanadaptablepathwayforachievingthe overallobjective• Definesmulti-disciplinaryinter-dependenciesforcoordinatedprojectmanagement andinformeddecisionmaking
Niamh Kinsella CMC&RegulatoryExpert
Paul Chamberlain Biopharmaceuticals&ImmunogenicityExpert
Jenny Sims NonClinicalExpert
Paula Salmikangas ATMPExpert
Josefin-Beate Holz ClinicalExpert
Steps to Phase 1 Clinical Development
Value Proposition
When to Start
Mapping the risks and value inflection points
The NDA Early Development Group
The Stage-Gate Approach for Early Development
• Definingthepathtowardscriticalmilestones,timelyexecutionandbalancingrisksand resourcesisakeystrategicfocusforsmalltomediumenterprises• Strategicroadmapintegratesprojectspecificdevelopmentstrategiesandmilestone deliverablesinoverallcorporateobjectivesandallowsaccelerationofhighvalueprojects• Question-baseddefinitionofstage-gatecriteriaoptimizesefficiencyofproductdevelopment, avoidsbackwardstepsandalignswithregulatorypriorities• Differentiatedproductsthatsatisfytherequirementsofthemajorregulatoryauthoritiesinall relevantregionswillbemoreattractive.Andsuchproductswillalsomaximisetheopportunity forgainingadditionalfundingandprovideattractiveexitopportunitiesforSMEs• Implementingaglobalandvalue-drivenperspectiveinearly-stagedevelopmentisakeydriver inpositioningtheproducttowardssuccessfulglobalapprovalandcommercialization
• DefiningaTargetProductProfileforthepotentialdrugcandidateisagreatstartingpointto delineateanearlydevelopmentstrategy• Go/No-Gocriteriaaswellasmilestonesanddeliverablescanbemappedoutaspartof astage-gateapproach
• Startingfromtheavailabledata(in-houseandexternal),astage-gateapproachcanbeapplied usingcriticalinputandassessmentofalternativeroutesforproductdevelopment• Aclearandacceptableproductprofilewitharoadmaptovalueinflectionpoint(s)allows proactivemitigationofchallengesandgaps• Earlyassessmentofbenefit/riskcanbeconductedwhichisfurtherdevelopedthroughthe developmentlifecycle• Consistent,clearproductmessages,identificationofsupportingdataandtheidentificationof common(core)requirementswillresultinacoredossierfortheEUandUS• Thiswillinturnachieveaccelerationofdevelopmenttimelines,focussingofresources andincreasingthevalueoftheproduct
Preclinical Development Phase 1
Development7 - 10 Years
Research2 - 4 Years
Discovery1 - 2 Years
MA
RKET
ING
Value-driven strategic roadmap
Commercialviabilityof proposedtarget&indication?
Adequatequalityand productivityachieved?
Allpertinentrisksevaluated inrelevantmodels?
Whichmolecularformat isoptimal?
Dose-andconcentration-response relationships?
Positivebenefit-to-riskfor administrationtohumans?
Evidenceoftherapeuticeffect intargetpopulation?
Opportunity Analysis
Developability
IND-enabling Safety Studies
Lead candidate selection
Translational Strategy
First-Time-in-Human
Clinical Proof-of-Concept
Cell line development
Process and formulation
development
Phase 1 process
developmentPhase 1
IMP supplyOn-going process
development
Analytical development
Quality Target Product Profile Development
Release testing / Stability testing /Characterisation
Animal species / model selection
In vitro assay development
PK-PD-ADA assay
development
Phase 1–enabling preclinical
studies
Translational PK-PD-toxicity relationships
Phase 2/3/MAA–enabling nonclinical studies
Target Product Profile Development
Risk Mitigation and Management
Phase 1 Clinical Trial
Phase 1 protocol
development
Clinical assay development
Agency Meetings CTA/IND CTA/IND
Maintenance
CMC
Non - Clinical
Regulatory
Clinical
Activity10,000
Safety100
Efficacy50
NDA10
ND2
RISK
VALU
E
Development Hurdles
STA
RT