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

?

$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