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Disruptive Innovation at the NIH
Kathy Hudson, Ph.D.
Deputy Director
Science, Outreach, and Policy
National Institutes of Health
“Science in pursuit of fundamental knowledge about the nature and behavior of living systemsand the application of that knowledge to extend healthy life and reduce the burdens of illness
...
NIH: Steward of Medical and Behavioral Research for the Nation
and reduce the burdens of illness and disability.”
NIH FY 2012 President’s Budget Request$31,987 MillionIncrease of $ 745 M or 2.4% over FY 2010 Actuals
$25
$30
$35
$40
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$0
$5
$10
$15
$20
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
2011 C
R
2012 P
B
ARRA Program Level
Note: ARRA funds were appropriated in FY 2009
Managing in Uncertain Times
• Operating at FY 2010 levels for 5+ months
• Threat of reduction to 2008 levels or worse
• Many new members are unfamiliar with biomedical research
• Threat of government shut down when current CR • Threat of government shut down when current CR expires
• Planning for flat budgets
House-passed HR 1
• Reduce NIH funding by $1.63 billion (-5.2%)
below the FY 2010 level
• -$639.5 million in pro rata reduction across all NIH ICs
• -$260 million (-2%) reduction to existing non-competing continuation awards for Research Project Grants,continuation awards for Research Project Grants,eliminating inflation costs
• Directive to support a minimum of 9,000 new and competing RPGs
• Mandated cap of $400,000 on average grant size
• -$48.5 million (-8.9%) for the NIH Common Fund, reducing it to the FY2008 level.
“Cutting the deficit by gutting our investments in innovation and education is like lightening an overloaded airplane by removing its engine.
It may make you feel like you're flying high at first, but it won't take long before you feel the impact.”
removing its engine.
— President Barack Obama, 2011 State of the Union
NIH Investments in Innovation — FY 2012
• Advancing Translational Sciences
• Accelerating Discovery Through Technology
• Enhancing the Evidence Base for Health-Care Decisions
• Encouraging New Investigators and New Ideas• Encouraging New Investigators and New Ideas
Therapeutics Development at NIH
• A 2010 trans-NIH inventory of activities relevant to therapeutics development found:– Substantial investments in therapeutics development research
– Approximately 65% for preclinical research; 35% clinical research
– 550 activities reported of varying sizes and areas of emphasis
Drugs
Distribution of Investment
RESULTS
We found that during the past 40 years, 153 new FDA-approved drugs, vaccines, or
new indications for existing drugs were discovered through research carried out in
PSRIs.PSRI-discovered drugs are expected to have a disproportionately large
therapeutic effect.
Valley of Death
New Medicines in your Medicine Cabinet:New Molecular Entities Entering Marketplace
30
40
50
60
0
10
20
30
Source: FDA
Most Candidate Compounds
Ultimately Prove Ineffective
- Pharmaceutical Research and Manufacturers of America; FDA
FDA Re-view
Ph. IIIPh. II Ph. IDisease Target
IDAssay Dev.
HTSProbe
to Lead
Pre-Clinical
FDA IND
PGxPh. IV
Scientific Management Review Board (SMRB)Recommendations to NIH
• May 2010
– SMRB asked to determine how NIH could better support translational and therapeutic sciences.
• December 2010 • December 2010
– SMRB recommends (12 to 1) that a new translational medicine and therapeutics center be created.
– SMRB also recommends NIH undertake a more extensive and detailed analysis through a transparent process to evaluate the new center’s impact.
Creation of theNational Center for Advancing Translational Sciences (NCATS)
To advance the discipline of translational science
and catalyze the development and testing of novel
diagnostics and therapeutics across a wide range diagnostics and therapeutics across a wide range
of human diseases and conditions
NCATS: Challenges and Opportunities
• Deluge of new discoveries of potential targets
• Unmet therapeutic needs for many conditions, especially rare and neglected diseases
• Need to view drug development pipeline as a scientific • Need to view drug development pipeline as a scientific problem – ripe for experimentation and process engineering
NCATS: Functions
• To improve the processes in the therapeutics development pipeline by:
– Experimenting with innovative approaches along the pipeline through an open-access model
– Choosing compelling therapeutic projects that can serve to evaluate those novel methods as they move through the pipeline
– Promoting and facilitating interactions with regulatory agencies to advance the field of regulatory science
NCATS: Functions
• To catalyze the development of novel diagnostics and therapeutics by:
– Facilitating and supporting partnerships and collaborations across all sectors
– Providing resources to enhance and enable the development of therapeutics
– Enhancing training in disciplines that are relevant to translational sciences
FDA Re-view
Ph. IIIPh. II Ph. IDisease Target
IDAssay Dev.
HTSProbe
to Lead
Pre-Clinical
FDA IND
PGxPh. IV
Quantitative High Throughput Screening
• Constriction point: traditional HTS at a single concentration– High false-positive hit rate requires extensive confirmatory
screening
– Many false negatives result in missed opportunities
• Process engineering
– Seven concentrations of each compound screened
– Decreases time to medicinal chemistry by 6 months
• Next step– Promote adoption
FDA Re-view
Ph. IIIPh. II Ph. IDisease Target
IDAssay Dev.
HTSProbe
to Lead
Pre-Clinical
FDA IND
PGxPh. IV
Pre-Clinical Toxicity Testing
GI
Endocrine
Cardiovascular
Skin
Constriction point: low concordance between animal and human toxicity
0 20 40 60 80 100
Other
Urinary
Neurological
Hepatic
Hematopoietic
% of compounds judged safe in animals that are non-toxic in humans
Nature Reviews Drug Discovery 3, 227-236, 2004
Towards Predictive ToxicologyProcess engineering
• Current investments
– High-throughput assays and tests in lower animal species
– High-throughput whole genome analytical methods on cell-based systems
• Proposed investments• Proposed investments
– iPS technology as in vitro models of human organ systems
– Retrospective analyses of trial data to develop prospective risk assessors
NCATS will:
• Facilitate – not duplicate – the translational research activities supported and conducted by the ICs
NEI
NCI NHLBI NIAID
NIDCR
NIH Institutes and Centers
NIDDKNIAMS
NIDA
CC
OD
NIA
NIDDK
CIT
NIEHS
NIMH
NINDS
NCCAM
NIMHD
NIDCD
NIGMSNINR
NIAAA
NICHD
NLM
NHGRI
FIC
NIBIB
CSR
NCATS
NEI
NCI NHLBI NIAID
NIDCR
Catalyzing Collaborations Within NIH
NIDDKNIAMS
NIDA
CC
OD
NIA
NIDDK
CIT
NIEHS
NIMH
NINDS
NCATS
NCCAM
NIMHD
NIDCD
NIGMSNINR
NIAAA
NICHD
NLM
NHGRI
FIC
NIBIB
CSR
NCATS will:
• Facilitate – not duplicate – the translational research activities supported and conducted by the ICs
• Complement – not compete with – the private sector
Catalyzing Collaborations With External Partners
NIH
Biotech
Academia
AdvocacyGroups
NIHTranslational
Sciences
FDA
PharmaNon-
Profits
NCATS will:
• Facilitate – not duplicate – the translational research activities supported and conducted by the ICs
• Complement – not compete with – the private sector
• Reinforce – not reduce – NIH’s commitment to basic • Reinforce – not reduce – NIH’s commitment to basic science research
NCATS Research Programs
• Components of Molecular Libraries Program
• Therapeutics for Rare and Neglected Diseases
• Office of Rare Diseases Research
• Rapid Access to Interventional Development
• Clinical and Translational Science Awards
• FDA-NIH Regulatory Science
• Cures Acceleration Network
NIH Therapeutics for Rare and Neglected Diseases (TRND) Program
• Congressionally-mandated effort to speed development of new drugs for rare and neglected diseases
• Collaboration between NIH-intramural and extramural labs
with appropriate expertise
• Projects will:• Projects will:
– Enter TRND at a variety of stages of development
– Be taken to phase needed for external organization to adopt
for clinical development
– Not duplicate pharma projects
• TRND will encourage creative partnerships; novel
approaches to intellectual property
TRND Pilot Projects
Disease Type Pathology CollaboratorsCompound
typeStage
Niemann-Pick Type C
Rare CNS,
liver/spleen
Disease Fnd, Extramural, Intramural
Repurposed approved
drugPreclinical
Sickle Cell Rare Blood
Biotech, NME
IND-enabling studies &
DiseaseRare Blood
IntramuralNME
clinical trials design
Chronic Lymphocytic
LeukemiaRare Cancer
Disease Fnd,
Extramural
Repurposed approved
drugPre-IND
Hereditary Inclusion Body
MyopathyRare Muscle
Biotech, Intramural
Intermediate replacement
IND-enabling studies
Schistosomiasis, Hookworm
NeglectedInfectious parasite
Extramural NMELead
optimization
FDA Re-view
Ph. IIIPh. II Ph. IDisease Target
IDAssay Dev.
HTSProbe
to Lead
Pre-Clinical
FDA IND
PGxPh. IV
NCATS Research Programs
• Components of Molecular Libraries Program
• Therapeutics for Rare and Neglected Diseases
• Office of Rare Diseases Research
• Rapid Access to Interventional Development
• Clinical and Translational Science Awards
• FDA-NIH Regulatory Science
• Cures Acceleration Network
Clinical and Translational Science Awards55 CTSA sites in 29 states
NCATS Research Programs
• Components of Molecular Libraries Program
• Therapeutics for Rare and Neglected Diseases
• Office of Rare Diseases Research
• Rapid Access to Interventional Development
• Clinical and Translational Science Awards
• FDA-NIH Regulatory Science
• Cures Acceleration Network
Cures Acceleration Network (CAN)
• Established by the Affordable Care Act
• CAN will
– Advance the development of “high need cures”
– Reduce barriers between research discovery and clinical trials in areas that the private sector is unlikely to pursue in an adequate or timely wayor timely way
• Review Board advises NIH Director– 24 members, including representatives from academia,
private industry, and patient advocacy groups
Cures Acceleration Network:Funding Mechanisms
• Grant Awards:– Up to $15 million per award per fiscal year
• Partnership Awards:– $1 match for every $3 from NIH
– Up to $15 million per award per fiscal– Up to $15 million per award per fiscal
• Flexible Research Awards: – DARPA-like authority
– Not to exceed 20% of total appropriated funds in any fiscal year
“To win the future, America needs to out-educate, out-innovate, and out-build the rest of the world.”
— President Barack Obama, Weekly AddressFebruary 5, 2011
Tell us what you think… www.nih.gov
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