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Drug Discovery and Delivery/ 3 Bioprocessing (D B) 4 Corners Alliance March 8-9, 2007 Kansas City 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 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 Group Expertise (cont.) Charles Decedue: Higuchi Bioscience Center--KU Drug discovery & development Lead compound to Phase I clinical trials Drugs on market 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) 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 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 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 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 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 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 General Observations (cont.) Realistic outcome = program project at NIH 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 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 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 Theme for the Alliance No. 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 Theme for the Alliance No. 1: Infectious Agents (cont.) Translational research Getting to Phase I clinical trials Collaborate on translation Economic development Theme for the Alliance No. 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 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 Large-scale Infrastructure Needs GLP Centralized screening facility? Large structured core service? 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 Funding Opportunities (cont.) CDC MRCE (Wash. U.) For Kansas, Nebraska, Iowa, Missouri, and Cleveland Up to $1.5 million Vaccines An Opportunity Personalized medicine Won’t be big pharma Small boutique companies spun out of universities More dreaming Other Infectious Disease Centers Emory? UW—focused on pediatric diseases Who would fund such a center? Who will play? KU Lawrence, KUMC, NU, MU, KSU Expertise and Strength of Each Participant Infectious diseases being researched Tularemia HIV Botulism Gram positive (sepsis) West Nile E. coli Salmonella Expertise and Strength of Each Participant (cont.) Technology/process facilities Faculty research 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 Likely Significant Competitors Nobody and everybody Biotech startups What Value does the Alliance Add? Infectious disease research Proposals in name of the Alliance Shared campus resources People 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) 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 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 Pooled Political Capital Yes 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 Action Plan (cont.) Who will carry out the plan? The Group? Who will monitor and prompt success? Alliance VPR steering committee 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 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 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 Vision (cont.) Alliance will naturally spread to other drug discovery areas Need focus to get it started Summary Description of Themes/Topics Selected Infectious diseases Not limited in reality Can do other drug discovery efforts Pathway to clinical trials