SM Paul, et al., Nature Reviews, Drug Discovery 2010

1. Major challenges • Cost-constraints in health care • Looming patent expirations • Complex regulatory environment • Falling R&D productivity SM Paul, et al., Nature Reviews, Drug Discovery 2010

2. Major challenges • Cost-constraints in health care • Looming patent expirations • Complex regulatory environment • Falling R&D productivity • Cost for each drug that wins approval for sale • by the FDA is about $1.2B SM Paul, et al., Nature Reviews, Drug Discovery 2010

3. SM Paul, et al., Nature Reviews, Drug Discovery 2010

4. SM Paul, et al., Nature Reviews, Drug Discovery 2010

5. Reducing either Phase II or Phase III CT by 50% from a baseline value of 2.5 years to 1.25 years would reduce the C per NME by about $200 million SM Paul, et al., Nature Reviews, Drug Discovery 2010

6. NINDS / NeuroNEXT • Accelerated phase II clinical trials for CNS • decrease the time/cost of P2 trials • Novel trials consortium: 25 sites across US • established clinical trials infrastructure • pre-existing master trial agreements for all 25 sites • central IRB review administered through NeuroNEXT CCC • expedited review/submission

7. UCLA University of Cincinnati University of Colorado, Denver University of Iowa (DCC) University of Kansas University of Miami University of Pittsburgh University of Rochester University of Utah University of Virginia University of Texas, Dallas Vanderbilt University Washington University in St. Louis Albert Einstein College of Medicine-Yeshiva Columbia-Cornell Emory Massachusetts General Hospital (CCC) Northwestern University Ohio State University Oregon Health and Science University Swedish Neuroscience Institute SUNY (Buffalo, Downstate, Upstate, and Stony Brook) University of Alabama, Birmingham University of California, Davis

8. Industry Approach to NeuroNEXT • Traditional U01- standard timelines • Small business grant- standard timelines • Resource Access Award (X01) • allows industry access to NeuroNEXT infrastructure • pre-existing master trial agreements for all 25 sites • central IRB review administered through NeuroNEXT CCC • expedited review-submission dates every two months • NINDS provides infrastructure • industry partner provides clinical funding

9. Applications must include • Compelling scientific evidence for proposed investigational agent • Proposed methodology for testing expected biological effect • Clinical protocol • Documentation of an active IND/IDE

10. Applications do not include • Investigator Brochures • CMC information • Safety toxicology information • Clinical pharmacology information other than justification of the proposed dosing regimen

11. NeuroNEXT Decisions • Special Emphasis Panel • “no-go” decisions for use of the network will be relayed to the applicant as soon as they are made • “go” decisions, which entail layers of review, may be given 4 months after formal receipt of the application

12. IP OPTIONS for RESOURCE ACCESS AWARD (X01)

13. NeuroNEXT-Contacts • Elizabeth McNeil (general information on NeuroNEXT) mcneilde@ninds.nih.gov • Heather Gunas (information on CRADAs, materials transfer agreements) GunasH@ninds.nih.gov • Laurie Arrants (information on CRADAs, materials transfer agreements) ArrantsL@ninds.nih.gov • www.ninds.nih.gov/NeuroNEXT