Partnerships with NIH to Advance New Technologies

1. Partnerships with NIH to Advance New Technologies Cindy K. Fuchs, J.D. Director, Technology Advancement Office, NIDDK Lili M. Portilla, M.P.A. Director, Office of Strategic Alliances, NCATS AIPLA 2012 Annual Meeting

2. NIH Translational Research Resourcesfor Advancing Early Stage Technologies Cindy K. Fuchs, J.D. Director, Technology Advancement Office, NIDDK Disclaimer: The information presented herein is not intended to be and should not be construed as legal advice.

3. Translational Research Process Product Regulatory Approval Clinical Trials Preclinical Development Lead Compound OptimizationScreen for Activity(Dr. Gold identified known drugs but no novel compounds) Assay Development Target Validation Identify Molecular Target 1 New Medicine 10,000 Molecules

4. Common Translational Research Needs • R&D Plan: unmet need, full commitment, resources and capabilities (HTS, medchem, relevant models, broad team-based expertise) • IP Package: convert a basic research discovery into a marketable product with a strong IP portfolio to protect R&D investment • Pre-clinical Package: de-risk technology (lead optimization, toxicity, efficacy, etc.) to prove clinical relevance and incentivize commercial investment

5. Drug Discovery Academia Basic Science: Identification of Molecular Pathways Lead to Pre-clinical Candidate Early Discovery Clinical Trials Pre-clinical Development Hit to Lead Target Identification Target Validation New Medicine Biotech/Pharma Companies Preclinical and Clinical Development Validated Hits Assay Development Drug Candidate Lead Commercial Partnering Interest Has Shifted1 Early Stage Research Discovery-->Pre-Clinical/Clinical Success PROOF of Clinical Relevance Required ------------------------------------------> 1 Stewart, J., Campbell Alliance Dealmakers’ Intentions Survey 2012; Christini, A., Nat. Biotechnol.30, 933-936 (2012)

6. PROOF OF STRONG IP REQUIRED After Ariad v. Lilly (2010) • Patents are notawarded for discovering key mechanisms - no matter how groundbreaking • Broad patent claims should be supported by a representative number of working examples in specification • Filing an application too early (with incomplete written description) may reduce incentives for commercial partners

7. Options for Advancing Dr. Gold’s Technology Traditional patent licensing model - a broad mechanism of action claim not likely patentable under Ariad - create R&D plan: design and evaluate novel analogs - create IP package: file on novel analogs - create pre-clinical package: lead optimization, pharm-tox, efficacy, etc. New “drug re-purposing” model • new use of known drugs –> typically limited commercial potential exceptions: orphan drug status, new formulation (combination, delayed release, etc.), off-label use - highlights need for pre-competitive partnerships between academia, non-profits, govt. labs, FDA, industry

8. Current Focus on “Translational Research” K. Pienta, MD, Univ. Mich. Nature Publishing Group

9. NIH Translational Research Addresses Unmet Needs FDARegulatory Science Vaccines, Drugs, Diagnostics, Enhanced Facilities/Workforce HIV Therapies & Diagnostics Anti-Cancer Therapies & Diagnostics

10. NIH INTRAMURAL RESEARCH (NIH Laboratories) NIH EXTRAMURALRESEARCH (Grantees and Contractors) • Supports: • >3,000 institutions worldwide • >300,000 scientists & research personnel • Awards issued in over 100 countries • Basic Translational & Clinical Research • 90% of overall NIH budget • Supports: • Bethesda, MD; Arizona; Montana • 27 NIH Institutes & Centers • >6,000 scientists & research personnel • Basic Translational & Clinical Research • 10% of overall NIH budget Courtesy of OER/NIH

11. NIH Intramural Translational Resources NIH Intramural Laboratories – 27 Institutes & Centers (ICs) • Each IC has a unique mission and is organized by - disease (cancer, diabetes) - organ system (heart lung & blood, eye) -life stage (child health, aging) - scientific discipline (infectious diseases, genomics) • ICs employ world-class scientists - potential research collaborations - access to special patient populations - research tools (cell lines, antibodies, mouse models)

12. Accessing NIH Intramural Translational Resources • Managed by IC Technology Development Offices - Facilitate research partnerships, exchange of research materials, data and confidential information - Negotiate transactional agreements: • confidentiality agreements • clinical trial agreements • collaboration agreements, CRADAs - Evaluate new innovations from IC scientists for partnering or patenting - Provide strategic guidance to IC scientists on technology development - Create virtual teams to advance early stage R&D and prove clinical relevance • Contact Information - Handout

13. Accessing NIH Extramural Translational Resources • Managed by IC Extramural Scientific Program Officers - Financial: grants & contracts - In-Kind (via NIH contracts/grants): - Sample repositories - Screening - Preclinical development - Clinical trial networks • Specific Resource Program Information – Handout

14. For More Information… Handouts: • NIH Translational Research Resources • NIH Intramural Researchers • NIH Technology Development Offices Contact Information: cfuchs@mail.nih.gov http://www2.niddk.nih.gov/TechDev/Main-HomePage/

15. Catalyzing InnovationNIH National Center for Advancing Translational Sciences Lili M. Portilla, MPA Director of Strategic Alliances, NCATS AIPLA 2012 Annual Meeting

16. Creation of theNational Center for Advancing Translational Sciences (NCATS) • Established on December 23, 2011 • Part of Consolidated Appropriations Act 2012 (PL 112-74)

17. Pursuing Opportunities for Disruptive Innovation “To catalyze the generation of innovative methods and technologies that will enhance the development, testing, and implementation of diagnostics and therapeutics across a wide range of human diseases and conditions.”

18. NCATS Organization OFFICE OF THE DIRECTOR Christopher Austin, M.D. (Director) Kathy Hudson, Ph.D. (Acting Deputy Director) COUNCIL/ CAN BOARD OFFICE OF POLICY, COMMUNICATIONS & STRATEGIC ALLIANCES Lili Portilla, MPA (Acting Director) EXECUTIVE OFFICE Erin Shannon, M.B.A. (Acting Executive Officer) OFFICE OF GRANTS MANAGEMENT & SCIENTIFIC REVIEW Jane Steinberg, Ph.D. (Acting Director) OFFICE OF RARE DISEASES RESEARCH Stephen Groft, Pharm.D. (Director) DIVISION OF PRE-CLINICAL INNOVATION (Vacant) DIVISION OF CLINICAL INNOVATION Josephine Briggs, M.D. (Acting Director)

19. Development of New Therapeutics Is Slow, Expensive and Failure-Prone

20. Division of Pre-Clinical Innovation (DPI) • Therapeutics for Rare and Neglected Diseases (TRND) • Toxicology in the 21st Century (Tox21) • Bridging Interventional Development Gaps (BrIDGs) • Molecular Libraries Probe Production Center • RNA interference (RNAi) DPI currently has 300+ collaborations with investigators across the U.S. and around the world.

21. Approved drugs effective for new indications New drugs for untreatable diseases Drugs suitable for adoption for further development Predictive in vitro toxicology profiles Novel clinical trial designs Small molecule and siRNA research probes NCATS DPI: A Collaborative Pipeline Clinical development candidate Preclinical development candidate Project Entry Point Lead compound Unvalidated target Validated target Target assay Assay Dev Target Validation Probe/Lead Development Lead Optimization Preclinical Development Clinical Trials Target FDA approval I II III Probe Devel/NCGC RNAi Preclinical Development/TRND Assay , Chemistry Technologies BrIDGs FDA Collaboration DPI Systems Toxicology (Tox21) Repurposing Repurposing Paradigm/Technology Development Chemical genomics systems biology data Leads for therapeutic development Genome-wide RNAi systems biology data Deliverables More efficient/faster/cheaper translation and therapeutic development

22. Bridging Interventional Development Gaps (BrIDGs) Program • Model: Contract access collaboration between DPI and extramural labs (Formerly NIH-RAID Program) • Projects • Enter with clinical candidate identified • Any disease eligible • Gap analysis followed by data generation using DPI contracts to generate data necessary for IND filing • Exit at or before IND • Milestone driven • Therapeutic modalities: any (small molecules, peptides, oligonucleotides, gene therapy, antibodies, recombinant proteins) • Eligible Applicants • Academic (US and Ex-US), Non-Profit, SBIR eligible businesses

23. BrIDGs Highlights • 180 applications submitted since 2005 • 34 approved • 19 completed projects (two in FY12) • 12/12 submitted INDs approved • 5 projects in Phase 1, three in Phase II • 5 agents licensed during or after BrIDGs involvement

25. Therapeutics for Rare and Neglected Diseases (TRND) Program • Model: Comprehensive drug development collaboration between DPI and extramural labs with disease-area / target expertise • Projects • May enter at various stages of preclinical development • Disease must meet FDA orphan or WHO neglected tropical disease criteria • Taken to stage needed to attract external organization to adopt to complete clinical development/registration, max 2a • Milestone driven • Therapeutic modalities: small molecules, proteins • Serve to develop new generally applicable platform technologies and paradigms • Eligible Applicants • Academic, Non-Profit, Government Lab, Biotech / Pharma • Ex-U.S. applicants accepted

26. TRND Highlights • 14 projects through pilot phase & 2 public solicitations since 2009 • Mix of small molecules and biologics • Two innovative platform technologies • 3 investigational drugs taken into humans • CLL: IND filed with US FDA 7/12/11, approved 8/5/11 • Phase I trial commenced 9/11 • SCD: IND filed 10/14/11, approved 11/10/11 • Phase I trial commenced 12/11 • HIBM: Complete response filed 7/27/12, approved 8/24/12 • Phase 1 trial in patients commenced 9/13/12 • Initiated first natural history study • HIBM: NIH Clinical Center, 1st patient enrolled September 2011 • Every project is a unique Public-Private partnership • Many include foundation and patient advocacy input

27. TRND Portfolio

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29. Partnerships with NIH to Advance New Technologies If you wish to receive an electronic version of this presentation and/or referenced resources, please send your request to: MTA@niddk.nih.gov AIPLA 2012 Annual Meeting