Raj Long presented on regulatory challenges for dementia treatment development and proposed innovative regulatory approaches. Key challenges included the prolonged time required for R&D, uncertainties around classifying and measuring dementia, and regulatory variances between geographies. These factors increase costs and risks for pharmaceutical companies, deterring investment. To address this, Long suggested regulatory designations to expedite review, adaptive development and licensing models, increased international regulator collaboration, incentives for developers, and public-private partnerships to accelerate cure discovery by 2025. Current approaches were deemed insufficient given the high risks and costs of dementia R&D.

1. Global Dementia Legacy Event – London, 2014
Dementia Treatment in Pharmaceutical Research
Regulatory Challenges & Imperatives
Raj Long
Senior Regulatory Officer - Integrated Development
Global Health
Bill & Melinda Gates Foundation - London
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2. Pharmaceutical R&D Regulatory Decision Points
LabelDose Safety SurveillancePK* initial
human
safety
Animal
model
efficacy
Safety and
Efficacy
Drug and
target
Efficacy
DevelopmentResearch
Full DevelopmentEarly Development LaunchDiscovery
Post
Launch
Approval
Phase
III
Phase
IIb
Phase
IIa
Phase
I PoC
Pre-Clinical
Phase
Candidate
Selection
Phase
Every Step is a Regulatory Hurdle to Overcome –
Chronological, Duration >12 years & £££
R. Long - June 19th, 2014
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3. Regulatory Variances Example - Intravenous Dx Agent for AD
Development
Rationale
Same Indication
US FDA
• Single Application
• Review Dx Division
• Covered primarily by Dx and medicines
regulations
• PDUFA coverage
1 dose
2 Pivotal Studies
EMA
• Single Application
• Review CHMP ( same as for medicines)
• Covered by Medicines Regulations
2 doses
2 Pivotal Studies
Japan
• 2 Applications
• Device and Medicine, 3 Pivotal studies
Same Molecule
US
EU
Japan
R. Long - June 19th, 2014
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4. Regulatory Challenges
Key Challenge Impact
Ageing – prolonged time
process. Disease prediction,
diagnosis, treatment ,
monitor
 Too long for traditional R&D – high costs with high risks
 Should the regulatory environment reflect this …. Why?
Dementia
 Still somewhat of an unknown ‘quantity’ for both regulators & industry
 Defining the regulatory framework comes from ‘experience’
 Experience is limited and dispersed – many unknowns
Regulatory Variances by
Geography
 Not an Incentive for developers
 Costs /Risks
Regulatory/Clinical Guidelines
 Have we got the science correct ? Need to focus more on translational
research or disease modelling ?
Technology in Dementia
 Technology can play a key role – prediction, diagnostics, & monitoring.
Need awareness that technology is a moving goal post – potential challenge
for regulators
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1
4
5
2
R. Long - June 19th, 2014
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5. Dementia Regulatory Landscape
• Attrition is high in discovery & early development - RISK
• Clinical ‘unknowns’ poses regulatory strategy issue – RISK
– a single disease or multiple
– ‘black box’ of disease progression
– known ‘unknowns’ resulting in a lack of target mode of action
• Highly regulated platform and with variances –requiring
tailoring of ‘global’ R&D to a ‘local’ geography – RISK
High Risks + High Costs = Investment Deterrent
R. Long - June 19th, 2014
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Insight as to why only 3 drugs were launched in 15 years !!!

6. Innovative Regulatory Imperatives
1. Can Dementia merit a special regulatory category – e.g. HIV, Oncology, Orphan
drug designation. Target – expedited review
2. Explore ‘adaptive development design’ potentially leading to adaptive licensing.
E.g. Target approval with a robust Ph2 + dynamic disease modelling. Follow up
with a post approval commitment and bridge with a rigorous risk management plan
to safeguard efficacy/safety.
3. G7 Regulators sharing resource – split/twin/share logical components of the review
process. Confluence of resource, expertise and expedite the review time
4. Develop a series of regulatory incentives e.g. fee waivers/reduction, use of priority
vouchers e.g. Knight Therapeutics for Impavido (Leishamaniosis Disease)
5. Proof of Concept Study Pilot – Conduct a tripartite partnership of manufacturer,
regulators, developers and WHO to work together through the entire development
cycle e.g. Meningitis Vaccine in Africa
6. Global Fund – enable private/public partnership to catalyse G7 ambition to deliver a
cure/disease modifying therapy by 2025.
Cannot be Business as Usual …
R. Long - June 19th, 2014
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7. Disclaimer
•The views and opinions expressed in the above PowerPoint slides are those of
the individual presenter and should not be attributed to affiliates, or any
organization with which the presenter is employed or affiliated.
•These PowerPoint slides are the intellectual property of the individual
presenter and are protected under the copyright laws of the United Kingdom
and other countries. Used by permission.
R. Long - June 19th, 2014
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