Bill Matthew Director, Office of Translational Research; NINDS bill.matthew@nih

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICESNational Institutes of Health

National Institute of Neurological Disorders and

Stroke

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICESNational Institutes of Health

National Institute of Neurological Disorders and

Stroke

American Society for Experimental Therapeutics

Annual MeetingMarch 04-06, 2010

Therapeutic Development

Resources at NINDS

Bill MatthewDirector, Office of Translational Research; NINDS bill.matthew@nih.gov

1 -Matthew

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICESNational Institutes of Health

National Institute of Neurological Disorders and

Stroke

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICESNational Institutes of Health

National Institute of Neurological Disorders and

Stroke

Pipeline Principles: 101

Basic Research

Therapeutics

Raw Material & Pump

Block ValveStation Final Delivery

2 -Matthew

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICESNational Institutes of Health

National Institute of Neurological Disorders and

Stroke

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICESNational Institutes of Health

National Institute of Neurological Disorders and

Stroke

Translational Research: The process of using novel, basic research discoveries to develop clinical applications.

T1

T2

T1

bench

bedside

community3 -Matthew

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICESNational Institutes of Health

National Institute of Neurological Disorders and

Stroke

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICESNational Institutes of Health

National Institute of Neurological Disorders and

Stroke

Office of Clinical Research

Office of Translational Research

NINDS Extramural Research

4 -Matthew

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICESNational Institutes of Health

National Institute of Neurological Disorders and

Stroke

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICESNational Institutes of Health

National Institute of Neurological Disorders and

Stroke

Basic Research -Target ID

Assay Hit to LeadScreen for Hit

Proof of Principle

Lead Optimization

PreClincal Candidate – Safety/Tox

First in Human

Anti-Convulsant Screening Program

Exploratory/Developmental Projects in Translational ResearchCooperative Program in Translational Research

Translational SBIR

Blueprint Neurotherapeutics Grand Challenge

CounterACT

RAID: Rapid Access to

Interventional Development

Small Molecule

Optimization

Small Business Program: SBIR & STTR

Spinal Muscular Atrophy Project

Molecular Libraries

(Roadmap)

Assay Development (Roadmap)

Drug Discovery for

Nervous System

Disorders

NINDS/OTR Activities in Therapeutic Development: NINDS Multiple ICs

5 -Matthew

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICESNational Institutes of Health

National Institute of Neurological Disorders and

Stroke

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICESNational 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

• Screening performed via a contract mechanism using a 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

Jim Stablesjs131e@nih.gov

www.ninds.nih.gov/research/asp/index.htm 6 -Matthew

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICESNational Institutes of Health

National Institute of Neurological Disorders and

Stroke

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICESNational Institutes of Health

National Institute of Neurological Disorders and

Stroke

Exploratory/Developmental Projects in Translational Research

www.ninds.nih.gov/research/translational/index.htm

Goal: Develop in vivo animal proof-of-concept for efficacy

•Program (R21) primarily targets four tasks:

• 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

Tom Millertm208y@nih.gov

7 -Matthew

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICESNational Institutes of Health

National Institute of Neurological Disorders and

Stroke

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICESNational Institutes of Health

National Institute of Neurological Disorders and

Stroke

Cooperative Program inTranslational Research

www.ninds.nih.gov/research/translational/index.htm

Tom Millertm208y@nih.gov

Goal: Bring novel compounds and devices to the clinic

•Cooperative Agreement, Milestone-driven program• Significant staff involvement • Reviewed by therapy development experts

• IND/IDE by the end of the research project period

• 6 filed INDs and 3 Clinical Trials

8 -Matthew

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICESNational Institutes of Health

National Institute of Neurological Disorders and

Stroke

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICESNational Institutes of Health

National Institute of Neurological Disorders and

Stroke

Cooperative Program inTranslational Research U44 Small Business Awards

www.ninds.nih.gov/research/translational/index.htm

Goal: Facilitate Small Business development of neurotherapeutics

•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 Stewartrs416y@nih.gov

Tom Millertm208y@nih.govFor Translational

9 -Matthew

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICESNational Institutes of Health

National Institute of Neurological Disorders and

Stroke

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICESNational Institutes of Health

National Institute of Neurological Disorders and

Stroke

THE SMA PROJECT

Goal: Develop a safe and effective drug for SpinalMuscular 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

www.smaproject.org

Jill Heemskerkjh440o@nih.gov

Coming Very Soon

10 -Matthew

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICESNational Institutes of Health

National Institute of Neurological Disorders and

Stroke

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICESNational 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: medicinal chemistry, pharm/tox, phase I clinical trials

•www.grants.nih.gov/grants/guide/notice-files/NOT-NS-10-002.html

Jill Heemskerkjh440o@nih.gov

Coming Very Soon

11 -Matthew

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICESNational Institutes of Health

National Institute of Neurological Disorders and

Stroke

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICESNational Institutes of Health

National Institute of Neurological Disorders and

Stroke

Goal: To develop safe and effective therapies and diagnostic technologies for victims of emergency incidents involving exposure to highly toxic chemicals

CounterACT Countermeasures Against Chemical Threats

David Jett jettd@ninds.nih.gov

www.ninds.nih.gov/counteract

• 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

12 -Matthew

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICESNational Institutes of Health

National Institute of Neurological Disorders and

Stroke

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICESNational Institutes of Health

National Institute of Neurological Disorders and

Stroke

www.ninds.nih.gov/research/molecular_libraries/index.htm

Mark Scheidelerscheidererm@ninds.nih.gov

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

13 -Matthew

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICESNational Institutes of Health

National Institute of Neurological Disorders and

Stroke

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICESNational Institutes of Health

National Institute of Neurological Disorders and

Stroke

NIH-RAIDNIH Rapid Access to Interventional Development

• 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 Millertm208y@nih.gov

www.nihroadmap.nih.gov/raid

Goal: To execute IND-enabling studies for extramural projects

14 -Matthew

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICESNational Institutes of Health

National Institute of Neurological Disorders and

Stroke

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICESNational Institutes of Health

National Institute of Neurological Disorders and

Stroke

Basic Research -Target ID

Assay Hit to LeadScreen for Hit

Proof of Principle

Lead Optimization

PreClincal Candidate – Safety/Tox

First in Human

Anti-Convulsant Screening Program

Exploratory/Developmental Projects in Translational ResearchCooperative Program in Translational Research

Translational SBIR

Blueprint Neurotherapeutics Grand Challenge

CounterACT

RAID: Rapid Access to

Interventional Development

Small Molecule

Optimization

Small Business Program: SBIR & STTR

Spinal Muscular Atrophy Project

Molecular Libraries

(Roadmap)

Assay Development (Roadmap)

Drug Discovery for

Nervous System

Disorders

NINDS/OTR Activities in Therapeutic Development: NINDS Multiple ICs

15 -Matthew

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICESNational Institutes of Health

National Institute of Neurological Disorders and

Stroke

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICESNational 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 SERVICESNational Institutes of Health

National Institute of Neurological Disorders and

Stroke

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICESNational Institutes of Health

National Institute of Neurological Disorders and

Stroke

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 Small Business Innovation Research (SBIR) Cooperative Agreements

U54 Specialized Center--Cooperative Agreements

X01 Resource Access Award

grants.nih.gov/grants/funding/funding_program.htm