U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
National Institute of Neurological Disorders and Stroke
American Society for
Experimental Therapeutics
Annual Meeting
March 04-06, 2010
Therapeutic
Development
Resources at NINDS
Bill Matthew
Director, Office of Translational
Research; NINDS
bill.matthew@nih.gov
1 -Matthew
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
National Institute of Neurological Disorders and Stroke
Pipeline Principles: 101
Raw Material
& Pump
Basic
Research
Block Valve
Station
Final Delivery
Therapeutics
2 -Matthew
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
National Institute of Neurological Disorders and Stroke
T1
bench
T1
Translational Research:
The process of using novel,
basic research discoveries
to develop clinical
applications.
bedside
T2
community
3 -Matthew
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
National Institute of Neurological Disorders and Stroke
NINDS Extramural Research
Research Clusters
Channels,
Synapses &
Circuits
Neural
Environment
Systems &
Cognitive
Neuroscience
Repair &
Plasticity
Neurodegeneration
Neurogenetics
Office of Translational Research
Office of Clinical Research
4 -Matthew
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
National Institute of Neurological Disorders and Stroke
NINDS/OTR Activities in Therapeutic Development:
Basic
Research Target ID
Assay
Screen for
Hit
Hit to Lead
Proof of
Principle
NINDS
Lead
Optimization
Multiple ICs
PreClincal
Candidate –
Safety/Tox
First in
Human
Anti-Convulsant Screening Program
Exploratory/Developmental Projects in Translational Research
Cooperative Program in
Translational Research
Translational SBIR
Small Business Program: SBIR & STTR
Spinal Muscular Atrophy Project
Blueprint Neurotherapeutics
Grand Challenge
CounterACT
Assay
Development
(Roadmap)
Molecular
Libraries
(Roadmap)
Small
Molecule
Optimization
Drug
Discovery for
Nervous
System
Disorders
RAID: Rapid
Access to
Interventional
Development
5 -Matthew
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
National Institute of Neurological Disorders and Stroke
Anticonvulsant Screening Program (ASP)
Goal: To facilitate the development of drugs for patients
with epilepsy, resistant epilepsy and related CNS conditions
Jim Stables
• Screening performed via a contract mechanism using a
js131e@nih.gov
battery of seizure models
• Compounds are submitted by a broad base of Investigators: > 500 total
Industrial companies (~200)
Academic institutions (~300)
• ASP Database > 29,000 small molecules – SAR chemistry & biology
• Compounds in clinical development: currently six
• Contributed to the development of ten marketed anti-convulsant drugs
www.ninds.nih.gov/research/asp/index.htm
6 -Matthew
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
National Institute of Neurological Disorders and Stroke
Exploratory/Developmental Projects in
Translational Research
Goal: Develop in vivo animal proof-of-concept for
efficacy
• Program (R21) primarily targets four tasks:
Tom Miller
tm208y@nih.gov
• Creation and validation of screening assays
• Development of animal models of disease
• Identification of candidate therapeutics
• Development of preliminary animal efficacy data
• However, can be used for any preclinical
development task
www.ninds.nih.gov/research/translational/index.htm
7 -Matthew
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
National Institute of Neurological Disorders and Stroke
Cooperative Program in
Translational Research
Goal: Bring novel compounds and devices to the clinic
• Cooperative Agreement, Milestone-driven program
• Significant staff involvement
• Reviewed by therapy development experts
Tom Miller
tm208y@nih.gov
• IND/IDE by the end of the research project period
• 6 filed INDs and 3 Clinical Trials
www.ninds.nih.gov/research/translational/index.htm
8 -Matthew
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
National Institute of Neurological Disorders and Stroke
Cooperative Program in
Translational Research
U44 Small Business Awards
Goal: Facilitate Small Business development of
neurotherapeutics
Tom Miller
tm208y@nih.gov
For Translational
• Fast-Track (Phase I & II) and Phase II Applications
accepted
• Phase I - identical scope as translational R21
• Phase II - identical scope as translational U01
Randy Stewart
rs416y@nih.gov
www.ninds.nih.gov/research/translational/index.htm
9 -Matthew
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
National Institute of Neurological Disorders and Stroke
THE SMA PROJECT
Goal: Develop a safe and effective drug for Spinal
Muscular Atrophy
• Develop drugs that increase expression of SMN protein
deficient in SMA patients
• A ‘Virtual Pharma’ network of contracts for industry-style
drug development:
• medicinal chemistry
• in vitro testing
• pharmacological and toxicological studies
• animal model testing
• Industry-seasoned consultants and advisors to oversee
programs
Jill Heemskerk
jh440o@nih.gov
www.smaproject.org
10 -Matthew
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
National Institute of Neurological Disorders and Stroke
Blueprint Neurotherapeutics Grand Challenge
•Goal: Provide Medicinal Chemistry and Pharm/tox expertise
for developing new drugs for nervous system disorders
• Investigator-initiated drug starting points
• “Virtual Pharma” model of drug development
• Provide access to industry-standard services:
Jill Heemskerk
medicinal chemistry, pharm/tox, phase I clinical trials
jh440o@nih.gov
• Provide industry expertise and guidance on committees
• Develop licensing opportunities
• Advance compounds through phase I trials
• Investigator retains IP
• Entry Requirements: - Hit compound(s)
•- Primary screening assay
•- Secondary assays for biological validation
•www.grants.nih.gov/grants/guide/notice-files/NOT-NS-10-002.html
11 -Matthew
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
National Institute of Neurological Disorders and Stroke
CounterACT
Countermeasures Against Chemical Threats
Goal: To develop safe and effective therapies and
diagnostic technologies for victims of emergency
incidents involving exposure to highly toxic chemicals
David Jett
jettd@ninds.nih.gov
• Research Centers of Excellence
• Individual research projects at academic,
government and industry laboratories
• Cooperative Agreements, Milestone-driven
• Efficacy screening and preclinical services
contracts
• Interagency Agreements with DoD laboratories
www.ninds.nih.gov/counteract
12 -Matthew
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
National Institute of Neurological Disorders and Stroke
Assay Development: Molecular Libraries and
Imaging Roadmap Program
Goal: Develop assays to identify small molecule
interactions via high-throughput screening of
compound libraries, and to chemically optimize
active compounds as molecular probes
Mark Scheideler
scheidererm@ninds.nih.gov
www.ninds.nih.gov/research/molecular_libraries/index.htm
13 -Matthew
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
National Institute of Neurological Disorders and Stroke
NIH-RAID
NIH Rapid Access to Interventional Development
Goal: To execute IND-enabling studies for extramural projects
• Pre-IND studies
• All diseases
• Access to government expertise and contract resources
– Production, bulk supply, GMP manufacturing
– Pharmacokinetic/ADME studies
– IND-directed toxicology, and more
• 6 successful IND submissions and 4 clinical trials to date
Tom Miller
tm208y@nih.gov
www.nihroadmap.nih.gov/raid
14 -Matthew
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
National Institute of Neurological Disorders and Stroke
NINDS/OTR Activities in Therapeutic Development:
Basic
Research Target ID
Assay
Screen for
Hit
Hit to Lead
Proof of
Principle
NINDS
Lead
Optimization
Multiple ICs
PreClincal
Candidate –
Safety/Tox
First in
Human
Anti-Convulsant Screening Program
Exploratory/Developmental Projects in Translational Research
Cooperative Program in
Translational Research
Translational SBIR
Small Business Program: SBIR & STTR
Spinal Muscular Atrophy Project
Blueprint Neurotherapeutics
Grand Challenge
CounterACT
Assay
Development
(Roadmap)
Molecular
Libraries
(Roadmap)
Small
Molecule
Optimization
Drug
Discovery for
Nervous
System
Disorders
RAID: Rapid
Access to
Interventional
Development
15 -Matthew
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
National Institute of Neurological Disorders and Stroke
Please Contact us…
www.ninds.nih.gov
Thank you
16 -Matthew
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
National Institute of Neurological Disorders and Stroke
grants.nih.gov/grants/funding/funding_program.htm
Activity
Code
R01
Research Project
R21
Exploratory/Developmental Grants
R41
Small Business Technology Transfer (STTR) Grants - Phase I
R42
Small Business Technology Transfer (STTR) Grants - Phase II
R43
Small Business Innovation Research Grants (SBIR) - Phase I
R44
Small Business Innovation Research Grants (SBIR) - Phase II
U01
Research Project--Cooperative Agreements
U44
U54
Small Business Innovation Research (SBIR) Cooperative
Agreements
Specialized Center--Cooperative Agreements
X01
Resource Access Award