Session Two: Barriers to investment in research to find a disease modifying therapy or cure for dementia Dr Neil Buckholtz , Director of Neuroscience, the National Institute on Aging (NIA), National Institutes of Health (NIH)

1. Global Dementia Legacy
Event
Neil Buckholtz, Ph.D.
Director, Division of Neuroscience
National Institute on Aging
June 18, 2014

2. International Alzheimer’s Disease Research
Portfolio (IADRP)
• Developed by NIA in collaboration with Alzheimer’s Association.
• Will enable funders of Alzheimer’s research to coordinate
planning, leverage resources, avoid duplication, and identify
new opportunities.
• Will give the public a full picture of the scale of ongoing research
on AD both nationally and internationally.
http://iadrp.nia.nih.gov/cadro-web/

3.  CADRO is a three-tier classification system created by NIA and the Alzheimer’s Association to capture
the complete range of AD research
 First level of classification consists of seven categories: 5 research and 2 research resources-related:
 Category A – Molecular Pathogenesis and Physiology of Alzheimer’s Disease
 Category B – Diagnosis, Assessment and Disease Monitoring
 Category C – Translational Research and Clinical Interventions
 Category D – Epidemiology
 Category E – Care, Support and Health Economics of Alzheimer’s Disease
 Category F – Resources for the Research Community
 Category G – Consortia and Public Private Partnerships
 Each category is divided into “research topics”; many topics further divided into “research themes”
 Detailed classification will enable funders and researchers to identify research gaps, areas of
overlap/duplication of effort, and opportunities for collaboration with much greater specificity
http://www.nia.nih.gov/research/dn/international-alzheimers-disease-research-portfolio
Common Alzheimer’s Disease Research Ontology
(CADRO) Structure

4.  Web-based portal developed by NIA and the Alzheimer’s Association:
Alzheimer’s and related dementias research funded projects 2008 to 2012.
 Currently includes: Federal agencies (including NIH, AHRQ, CDC, AoA, VA and
DoD), Alzheimer’s Association, Alzheimer’s Drug Discovery Foundation, and
Alzheimer’s Research UK, Alzheimer’s Society UK, Alzheimer’s Society of
Canada, and Alzheimer’s Australia.
 Summer 2014: Additional funders (10) and 2013 data will be available on IADRP.
http://iadrp.nia.nih.gov/cadro-web/

5. 1. Amyloid
32%
2. Tau
6%
3. Presenilins
4%
4. ApoE and Lipids
9%
5. Brain
Circuits and
Synapses
7%
6. Neurogenesis Cell
Death
5%
7. Immunity and
Inflammation
10%
8. Bioenergetics
1%
9. Vascular/Metabolic
Factors
5%
10. Hormones
3%
11. Genetics
11%
12. Other Pathogenic
Mechanisms
7%
Proportion of ‘Category A’ Projects by Topic across All
Funding Organizations (2012)

6. 20%
30%
40%
50%
60%
70%
80%
90%
100%
2008 2009 2010 2011 2012
12. Other Pathogenic Mechanisms
11. Genetics
10. Hormones
9. Vascular/Metabolic Factors
8. Bioenergetics
7. Immunity and Inflammation
6. Neurogenesis Cell Death
5. Brain Circuits and Synapses
4. ApoE and Lipids
3. Presenilins
2. Tau
1. Amyloid
Changes in the Proportion of ‘Category A’ Projects by Topic
for All Funding Organizations (2008 - 2012)

7. Step 1
Funding organizations identify
their respective AD and AD-
related dementia projects
Step 2
Funding organizations provide
the IADRP Team with projects
in a designated excel template
or via links to projects online
along with specified data
elements and abstracts
Step 3
The IADRP Team codes
projects (via an automated
coding portal) using the
Common Alzheimer's Disease
Research Ontology (CADRO)
(http://www.nia.nih.gov/resea
rch/dn/cadro-outline)
Step 4
Funding organizations validate
the coding via the coding
portal
Step 5
Coded and validated projects
are uploaded into the IADRP
online database
(http://iadrp.nia.nih.gov)
Portfolio Analysis
All users can systematically
compare and analyze funding,
composition of research,
specific trends in funding over
time, geographic distribution
of projects, and overlapping
funding priorities
IADRP Submission Process

8. Accelerating Medicines Partnership
Alzheimer's Disease
Program
8

9. Why AMP? Why now?
Developing effective new medicines
takes too long,
costs too much
and fails too often.

10. AMP Pilots:
Alzheimer’s disease
Type 2 diabetes
Rheumatoid arthritis/systemic lupus
erythematosus

11. NIA Supported Secondary Prevention Trials
Identify biomarkers correlated with therapeutic benefit in pre-symptomatic trials
Proposal Description Principal investigator
Dominantly Inherited
Alzheimer Network Trials
Unit (DIAN-TU) Trial
• Phase II/III study to assess the
safety, tolerability, and biomarker
efficacy of gantenerumab and
solanezumab in mutation carriers
• Randall J. Bateman, WUSL
• Collaborating companies:
– Lilly
– Roche
– Alzheimer's Assoc.
– Avid Radiopharm.
– Cog State
The Alzheimer's Prevention
Initiative APOE4 Trial
• Testing an anti-amyloid drug (TBD)
in cognitively normal older
volunteers who are at increased risk
of developing late-onset Alzheimer’s
(APOE-e4 homozygotes)
• Eric Reiman, BANNER
• Pierre Tariot, BANNER
Alzheimer’s Disease
Cooperative Study Anti-
Amyloid Treatment in
Asymptomatic AD Trial (A4)
• Secondary prevention trial of
solanezumab in clinically normal
older people with biomarker
evidence of brain amyloid.
• Reisa Sperling, Harvard
• Paul Aisen, UCSD
© The Boston Consulting Group, Inc.

12. AMP Project A
• Supplement the imaging and fluid biomarker panels
already included in these three NIH-funded Phase II/III
registration trials in presymptomatic Alzheimer’s through
the addition of tau PET imaging, EEG measures, and
novel fluid biomarkers.

13. Amyloid and Tau PET imaging
K. Johnson HAI 2014

14. AMP Project B
• Apply integrated network analyses (RNA, proteomic,
other “omic” studies) in 2500 human AD brain samples to
identify biologic nodes and networks that are linked to
the development or progression of AD to identify new
targets for drug development.
• Create standardized open-source data structures and
formats to aid the accessibility and ease of analysis of
biological data in a manner not currently practiced in the
AD field.

15. Pathway discovery, validation and compound identification for Alzheimer's disease*
Phil De Jager (Contact PI) Broad Institute
David Bennett Rush University
Integrative Biology Approach to Complexity of Alzheimer's Disease*
Eric Schadt (Contact PI) Icahn Institute for Multiscale Biology at Mount Sinai & Dept of
Genetics and Genomics Sciences
A System Approach to Targeting Innate Immunity in AD*
Todd Golde (Contact PI) – University of Florida
Nathan Price – Institute for Systems Biology, Seattle
Nulifer Ertiken-Taner and Steven Younkin – Mayo Clinic Jacksonville
Funded Projects
Allan Levey (Contact PI) Emory University
Discovery of Novel Proteomic Targets for Treatment of Alzheimer's Disease*
Lara Mangravite and Stephen Friend –Sage Bionetworks
Administrative Supplements for Data Enablement and Data Integration

16. Projected AMP funding contributions
Disease area
Total project
funding ($M)
Total NIH
funding ($M)
Total
industry
funding ($M)
AD 135 67.6 67.4
T2D 58.4 30.4 28.0
RA/SLE 41.6 20.9 20.7
Total 235 118.9 116.1
Industry is also providing AMP with additional in-kind
contributions, e.g., clinical trials, drug, tracer, databases, etc.
© The Boston Consulting Group, Inc.

17. AMP Participation by Disease Area
Alzheimer's
disease Type 2 Diabetes RA, SLE & related
Industry
members
Government
members
Non-profit
members
© The Boston Consulting Group, Inc.