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