American Society for Experimental Therapeutics Annual Meeting March 04-06, 2010 Therapeutic Development Resources at N

1. American Society for Experimental TherapeuticsAnnual MeetingMarch 04-06, 2010 Therapeutic Development Resources at NINDS Bill MatthewDirector, Office of Translational Research; NINDS bill.matthew@nih.gov 1 -Matthew

2. Pipeline Principles: 101 Raw Material & Pump Block Valve Station Final Delivery Basic Research Therapeutics 2 -Matthew

3. T1 Translational Research: The process of using novel, basic research discoveries to develop clinical applications. bench T1 bedside T2 community 3 -Matthew

4. NINDS Extramural Research Research Clusters Channels, Synapses & Circuits Systems & Cognitive Neuroscience Neural Environment Repair & Plasticity Neuro-degeneration Neuro- genetics Office of Translational Research Office of Clinical Research 4 -Matthew

5. NINDS/OTR Activities in Therapeutic Development: Multiple ICs NINDS Basic Research -Target ID PreClincal Candidate – Safety/Tox Proof of Principle Lead Optimization First in Human Assay Screen for Hit Hit to Lead 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

6. Anticonvulsant Screening Program (ASP) Goal: To facilitate the development of drugs for patients with epilepsy, resistant epilepsy and related CNS conditions Jim Stables js131e@nih.gov • 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 www.ninds.nih.gov/research/asp/index.htm 6 -Matthew

7. Exploratory/Developmental Projects in Translational Research • 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 Miller tm208y@nih.gov www.ninds.nih.gov/research/translational/index.htm 7 -Matthew

8. Cooperative Program inTranslational 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

9. Cooperative Program inTranslational Research U44 Small Business Awards • 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 Tom Miller tm208y@nih.gov For Translational Randy Stewart rs416y@nih.gov www.ninds.nih.gov/research/translational/index.htm 9 -Matthew

10. 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 Coming Very Soon www.smaproject.org 10 -Matthew

11. 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 Jill Heemskerk jh440o@nih.gov Coming Very Soon • 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

12. 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

13. 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

14. 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 Goal: To execute IND-enabling studies for extramural projects Tom Miller tm208y@nih.gov www.nihroadmap.nih.gov/raid 14 -Matthew

15. Multiple ICs NINDS/OTR Activities in Therapeutic Development: NINDS Basic Research -Target ID PreClincal Candidate – Safety/Tox Proof of Principle Lead Optimization First in Human Assay Screen for Hit Hit to Lead 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

16. Please Contact us… www.ninds.nih.gov Thank you 16 -Matthew

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