Drug Discovery and Delivery/Bioprocessing (D3B)

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 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

Theme for the AllianceNo. 1: Infectious Agents (cont.)

Translational research Getting to Phase I clinical trials Collaborate on translation

Economic development

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

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