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
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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
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Drug discovery & development
Lead compound to Phase I clinical trials
Drugs on market
Group Expertise (cont.)
 Robert Powers: Structural biology, NMR,
bioinformatics—NU
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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
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“Molecules are us.”
Collaborates with bioscientists
Minnesota, Iowa State, and UMKC
collaborators
High throughput screening center
 120,000
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compound library
KU Pharmacy ranks #3 in NIH funding
Group Expertise (cont.)
 Wynn Volkert: Radiopharmaceutical
Science Institute—MU
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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
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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
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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
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Anti-malarials
Therapeutics for fungal infections
 Steve DiMagno
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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
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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
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Can you really sample the space?
Other ways to search/screen molecule candidates?
 High price of pharmaceuticals
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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
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Efficacy
Toxicity
 Challenge: find the 25 hERG like tests
for toxicity, ones with a history
Theme for the Alliance
No. 1: Infectious Agents
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Pharma has abandoned
Third world
Focus on humans
Pick a disease?
Don’t/can’t compete with big pharma
Universities
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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
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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
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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?
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Large structured core service?
Funding Opportunities
 Gates Foundation
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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
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Pre-symptomatic detection of disease
Quantum leap development
Funding Opportunities (cont.)
 CDC
 MRCE (Wash. U.)
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For Kansas, Nebraska, Iowa, Missouri, and
Cleveland
Up to $1.5 million
Vaccines
An Opportunity
 Personalized medicine
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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
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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
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Out source
 Models for lead development
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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
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Investment fund
State organizations?
Federal support?
 Paid leader of the effort
 Money
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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
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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
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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.
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Start with two faculty partnerships for
example and build up
Action Plan (cont.)
 Who will carry out the plan?
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The Group?
 Who will monitor and prompt success?
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Alliance VPR steering committee
Action Plan (cont.)
 Need Updated List of Expertise from the
campuses
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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
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On-campus rates charged to Alliance
members
 Proposals submitted in the name of the
Alliance
Vision (cont.)
 Alliance drug discovery core facilities
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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
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Not limited in reality
Can do other drug discovery efforts
 Pathway to clinical trials