Drug Discovery and Delivery/ Bioprocessing (D 3 B)

1. Drug Discovery and Delivery/Bioprocessing (D3B) 4 Corners Alliance March 8-9, 2007 Kansas City

2. Group Expertise • Bruce Schultz: Anatomy & Physiology—KSU • Target identification • Drug optimization • Kevin Van Cott: Bioprocessing Facility—NU • Protein to Phase I trials • Purification, characterization, etc. • cGMP pilot plant (10,000 sq.ft. due 2007) • Small biotechs/large pharma/NIH/DoD • Vaccines, therapeutics • Works with Russ Middaugh at KU • All money staff…limits pro bono work

3. Group Expertise (cont.) • Kathy Roby: Anatomy & cell biology/KU Cancer Center—KUMC • Transition to clinical trials • Ovarian cancer • Efficacy testing • No GLP/GMP = limitation • Scott Weir: leader and promotion of collaboration • Drug to clinical trial pathway

4. Group Expertise (cont.) • Charles Decedue: Higuchi Bioscience Center--KU • Drug discovery & development • Lead compound to Phase I clinical trials • Drugs on market

5. Group Expertise (cont.) • Robert Powers: Structural biology, NMR, bioinformatics—NU • Small molecule library • Robert came from the pharmaceutical industry (Wyeth) • Drug discovery/design • Metabolomics • High throughput NMR • NMR/mass spec technique (100’s a day)

6. Group Expertise (cont.) • Jeff Aube: medicinal chemistry, NIH CMLD Center—KU • “Molecules are us.” • Collaborates with bioscientists • Minnesota, Iowa State, and UMKC collaborators • High throughput screening center • 120,000 compound library • KU Pharmacy ranks #3 in NIH funding

7. Group Expertise (cont.) • Wynn Volkert: Radiopharmaceutical Science Institute—MU • Largest research reactor in the US • Radioisotopes • All domestic P32, etc. • Isotopes useful for therapy • NCI in vivo cellular and imaging center • Radio labeling • Peptides • Identifiable target vectors…use radio isotopes? • George Smith—large phage display library • 17 tesla small bore magnet

8. Group Expertise (cont.) • Dave VanderVelde: NMR Facility—KU • 800 MHz NMR…only in area until MU’s up • Smaller instruments for special uses • Natural products • High throughput screening • Solid state NMR

9. Group Expertise (cont.) • Joe Tash: male contraceptive--KUMC • Collaboration with KULC and Minnesota • MC developed from anti-cancer agent • Derivatives into library and anti-cancer candidates • Duke plus other universities • Came because the life science group was crowded and we “looked like a nice bunch” • 10.4 tesla small bore magnet in Hoglund imaging center

10. Group Expertise (cont.) • Pat Dussault: synthetic organic chemist—NU • Anti-malarials • Therapeutics for fungal infections • Steve DiMagno • Not present. Stuck in the bioenergy session. • Imaging techniques • PET

11. General Observations • Having the vet schools in the alliance • Swine at MU • Collaborate on compound management • Working issues with remote instrumentation, e.g. mice and small bore magnets • NIH has an R01 oriented culture • Difficulty in putting together a big idea

12. General Observations (cont.) • Realistic outcome = program project at NIH

13. Grand Challenges • Targeted therapy (molecule, tissue, tumor) • Individualized therapy • Identification of new novel targets • “Me too” approach of big pharma leaving potential targets behind (plus “me too” drugs) • Human genome project => drug targets • Infectious diseases • Big pharma won’t touch • Role for universities • Gates Foundation

14. Grand Challenges (cont.) • Expression regulation • Preventative medicine • Theoretical no. of possible compounds > no. of atoms in universe • Can you really sample the space? • Other ways to search/screen molecule candidates? • High price of pharmaceuticals • Reduce expenses getting to Phase I • Reduce the failure rate, e.g. novel tox technique

15. Grand Challenges (cont.) • Two most common failures in the clinic • Efficacy • Toxicity • Challenge: find the 25 hERG like tests for toxicity, ones with a history

16. Theme for the AllianceNo. 1: Infectious Agents • Pharma has abandoned • Third world • Focus on humans • Pick a disease? • Don’t/can’t compete with big pharma • Universities • KU(LC/MC)-molecules, natural products, probes • MU-technology, radio labeling, molecular imaging • NU-focus on entire organism, small molecule screening • KSU-looking across species, animal/tissue models

17. Theme for the AllianceNo. 1: Infectious Agents (cont.) • Translational research • Getting to Phase I clinical trials • Collaborate on translation • Economic development

18. Theme for the AllianceNo. 2: General Screening for Toxicity • Reduce the failure rate • Animal and cell model development • Universities • KULC/KUMC--Pharm & Tox • NU—metabolomics • MU—technology • Foundations • Not an existing strength • Longer term goal

19. Goals • Research • Spin off companies • Improving health of the public • Infectious disease center…part of the Alliance • NBAF support to one of the three Alliance locations

20. Large-scale Infrastructure Needs • GLP • Centralized screening facility? • Large structured core service?

21. Funding Opportunities • Gates Foundation • Priorities are infectious diseases • Gates not interested in basic research • Will fund distribution of the cure • Gates gave UCSF $20 million to research anti-diarrheals (Bill Gates connection to PI) • DARPA • Pre-symptomatic detection of disease • Quantum leap development

22. Funding Opportunities (cont.) • CDC • MRCE (Wash. U.) • For Kansas, Nebraska, Iowa, Missouri, and Cleveland • Up to $1.5 million • Vaccines

23. An Opportunity • Personalized medicine • Won’t be big pharma • Small boutique companies spun out of universities • More dreaming

24. Other Infectious Disease Centers • Emory? • UW—focused on pediatric diseases • Who would fund such a center?

25. Who will play? • KU Lawrence, KUMC, NU, MU, KSU

26. Expertise and Strength of Each Participant • Infectious diseases being researched • Tularemia • HIV • Botulism • Gram positive (sepsis) • West Nile • E. coli • Salmonella

27. Expertise and Strength of Each Participant (cont.) • Technology/process facilities • Faculty research

28. Needs, Weaknesses, or Conflicts • Surely you joke! • Lack of a major funding source • Building a portfolio a la Russ Middaugh at KU is difficult • Money • Cooperative spirit a plus

29. Likely Significant Competitors • Nobody and everybody • Biotech startups

30. What Value does the Alliance Add? • Infectious disease research • Proposals in name of the Alliance • Shared campus resources • People

31. Needed Support • Merged seed funds for Alliance specific collaborations • GMP • Out source • Models for lead development • Ad hoc seed funding • Core facility at one campus • Money from the Alliance (similar to way core facilities are funded on campus)

32. Needed Support (cont.) • Alliance Translational Fund • Investment fund • State organizations? • Federal support? • Paid leader of the effort • Money • Cash: $1,000,000 up front • Annual: • Salary/fringe = $200,000 per year (leader) • Cores = $250,000 per core

33. Needed Support (cont.) • Needed actions agreed to • 4 Corners Infectious Disease meeting • Grad student posters, etc. • Funding opportunities • Provide pooled seed funds to be awarded at meeting • Communications

34. Pooled Political Capital • Yes

35. Action Plan • Leadership • Scott Weir’s long-lost twin • Person designated on each campus • Outcomes/decisions agreed to • Form small groups of faculty participants • 4 Corners Infectious Disease Alliance • Work on model MOU, MTA, fees, etc. • Start with two faculty partnerships for example and build up

36. Action Plan (cont.) • Who will carry out the plan? • The Group? • Who will monitor and prompt success? • Alliance VPR steering committee

37. Action Plan (cont.) • Need Updated List of Expertise from the campuses • Update lists of expertise and make available • Need wider net • Target the response—infectious diseases

38. Vision • Operate through 4 Corners Alliance • Four Corners Infectious Disease Alliance (4CIDA) • Certain instruments/facilities declared part of Alliance • On-campus rates charged to Alliance members • Proposals submitted in the name of the Alliance

39. Vision (cont.) • Alliance drug discovery core facilities • Chemical libraries • Alliance high throughput screening • Unique animal models • Protein production facilities • Biotech facilities • Pre-clinical formulation • Instruments available locally • Need: Generic Material Transfer Agreement (MTA) for the Alliance

40. Vision (cont.) • Alliance will naturally spread to other drug discovery areas • Need focus to get it started

41. Summary Description of Themes/Topics Selected • Infectious diseases • Not limited in reality • Can do other drug discovery efforts • Pathway to clinical trials