1. Innovative Technology Transfer: Supporting a Strategic Delay Robert C. Bast, Jr., M.D. Vice President for Translational Research University of Texas M.D. Anderson Cancer Center

2. Supporting A Strategic Delay In Biomedical Science and Health Care, the Value of new Inventions increases Dramatically if they proceed to Successful Phase I Human Trials before Licensing Resources, Champions and Processes must be found to support Early and Mid-Stage Development, Particularly in Today’s Environment where Licensing can be Difficult Does JSC need this Capability?

3. DiscoveryDrug Development Preclinical Development Clinical Phase I Phase II Phase III Regulatory Approval Target Lead Identification Lead Optimization Market “GAP 1” Research funding Industry funding “GAP 2” Early-stage development License or Startup Funding Gaps Example Drug Development “GAP 3”

4. Definition The Funding Gap or The Valley of Death: –Government tends to fund basic research and a technology may have passed that stage and be too “applied” for further funding –The private sector will not yet pick up technology because it is too risky (has not been fully “applied” yet)

5. The Valley Of Death Valley of Death Existing Commercialization Resources Existing Research Resources Idea Research Fuzzy Front End Product Development Commercialization From: The PDMA ToolBook 1 for New Product Development

6. The Valley Of Death What are critical needs to bridge the gap –Critical resources Money Expertise Equipment: i.e. tooling, production, validation, computing,… –Champions Supportive experts –Formal process and pathways For example protection of IP, regulatory expertise, standardized processes for development and commercialization,…

7. DiscoveryDrug Development Preclinical Development Clinical Phase I Phase II Phase III Regulatory Approval Target Lead Identification Lead Optimization Market “GAP 1” Research funding Industry funding “GAP 2” Early-stage development License or Startup Early-Stage Gap Example Drug Development “GAP 3”

8. Early-Stage Gap Drugs Early gap is typically between promising first cell line and animal test results and further development of compound of interest –Optimization of compound (chemistry) –Lead compound selection –Formulation and pharmacokinetics –Dose ranging –Pre-IND (rodent) toxicology study –Pre-IND FDA call Cost range: $50K to $300K

9. Early-Stage Gap Devices Early gap is typically between first idea and concept and creation of functional prototype –Prototype development –Preparation regulatory documentation Cost range: $50K to $1,000,000

10. Mid-Stage Gap Drugs Mid stage gap is typically between pre-IND and conclusion of a Phase I trial –Second species toxicology study –IND preparation –Quality controls –Manufacturing drug for Phase I trial –Possibly Phase I trial –Costs to license a technology from an University (license costs and legal fees) Cost range: $300K to $3 million

11. Mid-Stage Gap Devices Mid stage gap is typically between prototype development and validation of the device/technology –Validation of function –Preliminary studies with animals or humans (samples) –Regulatory documentation Cost range: $100K to $ 2 million

12. DiscoveryDrug Development Preclinical Development Clinical Phase I Phase II Phase III Regulatory Approval Target Lead Identification Lead Optimization Market “GAP 1” Research funding Industry funding “GAP 2” Early-stage development License or Startup Late-Stage Gap Example Drug Development “GAP 3”

13. Late-Stage Gap Drugs Typically money to run Phase 2 and 3 clinical trials and comply with all FDA reporting requirements Cost range: tens to hundreds of millions Very complex Mostly financed by professional investors and industry

14. Late-Stage Gap Devices Finalizing FDA submission for device clearance Clinical studies for PreMarket Approvals (PMA’s) if needed Set up of manufacturing process Scale-up manufacturing Going to market after FDA clearance Cost range: can be very expensive

15. Value Increase of Drugs

16. University Funding Models Many universities and academic institutions have launched pre-seed and seed funds to bridge early-stage gaps Various models can be found –Managed by universities –Managed by investors –Combined models

17. Case Study: TRC Fund Gap funding by The University of Texas MD Anderson Cancer Center TRC = Technology Review Committee TRC fund managed by Office of Technology Discovery (Translational Research) Money comes from philanthropic sources and operational clinical margin

18. Case Study: TRC Fund Amounts invested: $10K to $250K Requirements –Invention Disclosure filed –Has to support hospital’s mission –Has to have commercial potential –Has to be scientifically sound Technology Review committee a mix of faculty and external experts –Venture capitalists, lawyers, CEOs biotech

19. Case Study: TRC Fund Inventor has to prepare –Funding request with Brief technology and IP summary Milestones Timelines Budgets 4 pages about technology background, scientific data, pictures of design or prototype design, description of software, … –Presentation to TRC committee

20. Project Flow (7 years) 1532 formal faculty contacts 81 project teams formed 51 projects presented 33 projects funded $ 2,134,913

21. Project Flow 14 6 5 8

22. Aerosolized Lung Immune Stimulant Dr. Burton Dickey New drug to prevent pneumonia in immuno- compromised cancer patients Prevent pandemic pneumonia (influenza, SARS, H1N1, etc.) Prevent and treat bioterror pneumonia –Plague, anthrax, others Startup company “Pulmotect” formed

23. Aerosolized Lung Immune Stimulant

24. Project financed with $ 75,753 Drug under development Value for MDACC: –New IP generated –Licensed to startup company Pulmotect $ 200K in-kind financing to start-up via AlphaDev –Grants: total $ 2,835,000 $ 25K (Lehman Brothers Foundation) $ 10K (Texas Ignition Fund TIF) $ 50K (NCI Spore) $ 200K (Living Legends Fund) $ 300K (Charles Culpeper Award) $ 250K Texas Emerging Technology Fund (ETF) $ 2 million (National Institute of Health NIH) –Several journal publications and abstracts

25. MRI Visible Seeds Dr. Steven Frank MRI is superior imaging technology for prostate than ultrasound and CT No MRI visible markers available Development of MRI marker Development of MRI visible brachytherapy seeds for treatment of prostate cancer

26. MRI Visible Seeds Seeds visible but unclear anatomy Seeds visible but CT artifacts Clear anatomy but no visible seeds

27. MRI Visible Seeds

28. MRI visible seed

29. MRI Visible Seeds Project financed with $ 148,000 Marker and MRI visible seeds developed Value for MDACC: –New IP generated –Not yet licensed (still underdevelopment) –Grants: total $ 280,000 $ 225K Frank (Prostate Cancer Foundation) $ 55K Frank (Texas Ignition Fund TIF) –Several journal publications and abstracts –$2 million external investments for Start-up

30. Value Creation TRC Projects 2003 to date License Income (license, option, fees)$ 1,361,470 SBIR’s, STTR’s$ 240,000 Sponsored Research Agreements (SRAs)$ 250,000 Research grants$ 4,773,000 Money saved by MDACC$ 1,322,000 Outside investments$ 4,530,000 Total Value Creation$ 12,476,470 (6XROI)

31. Other TRC Benefits New Invention Disclosures as result of funding14 Patents filed as result of funding9 Licenses/Options signed10/4 Startup companies formed / in formation5/4 Entrepreneurship courses organized and hosted5 Publications (incl. abstracts)57 Raised awareness for technology transfer and entrepreneurshipPricele$$

32. DiscoveryDrug Development Preclinical Development Clinical Phase I Phase II Phase III Regulatory Approval Target Lead Identification Lead Optimization Market “GAP 1” Research funding Industry funding “GAP 2” Early-stage development License or Startup Mid-Stage Gap Example Drug Development “GAP 3”

33. Supporting A Strategic Delay Does JSC need Additional In-House Capability to develop Inventions Prior to Licensing? Can the TMC help to identify Unmet Medical Needs that could be met with NASA Technology? Might the TMC Partner with JSC to develop Biomedical Devices and Processes prior to Licensing to the Private Sector?