An Academic Model to Bridge the Valley of Death April 17, 2009

1. An Academic Model to Bridge the Valley of DeathApril 17, 2009 Scott Weir, PharmD, PhD Institute for Advancing Medical Innovation University of Kansas

2. Aligning The Stars in Kansas Key Success Factors • Reducing Cancer Burden in Kansas • Ewing Kauffman Foundation • Drug Discovery, Delivery and Development • State Economic Impact • Academic, Industry and Disease Philanthropy Partnerships • Pharmaceutical industry expertise and best practices

3. Reducing Cancer Burden in Kansas Regional Problem: Cancer *Cancer patients must travel 200 to 700 miles to reach an NCI-designated Comprehensive Cancer Center • 25,700 citizens in Kansas and western Missouri diagnosed in 2008* • 11,028deaths in 2008* • Cancer mortality rate reductions in KS (-0.5%) and MO (-0.7%) lags national trend (-2.1%) • $4.3 Billion annually in medical expenses and lost productivity *American Cancer Society. Statistics for 2008.

4. Reducing Cancer Burden in Kansas NCI Designation Differentiators Drug Discovery, Delivery & Development Community-based Approach Prevention & Control Research Institute for Advancing Medical Innovation Clinical Trials Office Rural Primary Care Outreach Breast Cancer Prevention & Survivorship Centers Results More advanced cancer prevention, early detection, treatment, and survivorship

5. Ewing Kauffman Foundation Entrepreneurship • Largest foundation devoted to innovation and entrepreneurship • $16.2M over five years • Proof of Concept funding • Industry adjunct faculty • Project managers • Fellowships

6. Ewing Kauffman Foundation Institute for Advancing Medical Innovation Novel Drugs &Drug Targets Drug Products &DeliveryPlatforms Biomaterials & Medical Devices Drug-Device Combination Products Drug Discovery Research Drug DeliveryResearch Bio-EngineeringResearch IntegratedBio-Engineering& Drug Research Training the Next Generation Of Medical Innovators Advance Medical Innovations To Commercialization

7. Capitalizing on Pharmacy Strengths NIH Funding History Medicinal Chemistry Chemical Methodologies and Library Development Center Specialized Chemistry Center Faculty Pharmaceutical Chemistry Dr. Higuchi, The Father of Physical Pharmacy Alza Corporation founded at KU NCI formulation contract (Taxol®, Velcade®) Dr. Val Stella Drug Discovery, Delivery and Development

8. Reengineered Discovery Process Drug Discovery, Delivery and Development 10 – 18 months ~ 18 months Target -> Chemical Hit Chemical Hit -> Lead Lead -> DevelopmentCandidate • 1 • Target • Selection • & • Validation • Target • Production • 2 • 3 • High • Throughput • Screening • 4 • Chemical • Hit • Identification • 5 • Define Lead • Selection • Criteria • 6 • Prediction of • Physio- • Chemical • Properties • 7 • In vitro • Potency & • Selectivity • In vivo • Proof • of Concept • 8 • Early • ADMET • 9 • Pre – • Formulation • Screening • 10 • In vivo and • In vitro • ADMET • Profiling • 11 • Prepare for • IND • Enabling • Activities Novel Drug Target Development Candidate

9. Our Drug Pipeline 62 Projects 36 Cancer Projects

10. State Economic Impact Investors in Our Program • Faculty recruitment • Facilities • Facilitating collaborative research • R&D Infrastructure • Innovation centers • Federal grant matching • Heartland BioVentures • Drug Delivery Center of Excellence • Entrepreneurship training

11. Kansas Centric Big Picture State Economic Impact 3 Years 1 Year 6-8 Years 1.5 Yr Drug Discovery Early Stage Drug Development Late Stage Drug Development Product Registration • Target • Selection • & • Validation • HTS • Identified • Chemical • Hits • Optimized • Chemical • Lead • Candidates • Development • Candidate • Selected • GLP • Drug • Safety GMP Drug Substance & Product Mfg • IND • Prep • Submission • Filing Phase I Clinical Trial Phase II Clinical Trials Phase III Clinical Trials NDA Preparation Submission And Approval Commercialization Entity Within Universities Kansas Start-Up National Drug Development Accelerator

12. KU Researchers, Cores and Centers Advancing Innovations to Clinical Proof of Concept Disease Philanthropy Partners Pharma Partners NIH NCI Academic Partners Investors Partnerships Assembling the Bridge

13. Partnerships • “LLS, University of Kansas Cancer Center Announce Innovative Partnership to Accelerate Drug Development” • January 7, 2009 Press Release • Currently $1.5M in funding supporting two projects • Counts toward cancer-related research funding • April 22 Health Canada Pre-CTA Meeting

14. Partnerships “Institute for Pediatric Innovation Awarded Funding by University of Kansas to Analyze the Use of Extemporaneously Prepared Medicines in Children’s Hospitals” June 30, 2008 Press Release KU is the drug development partner with Beckloff Associates Inc. First pediatric product developed and ready for GMP manufacturing Kauffman Foundation grant funding development of two products annually

15. Pharmaceutical Industry Best Practices • Pharma “profiling” • Go/no go decisions • Pre-determined criteria • Industry experienced leadership and project management • High performance project teams • Cores and centers • Partnerships • Portfolio review and prioritization • Drug targets • Continuous pipeline review • Leveraging industry partners (e.g., GLP, GMP) • Integration of intellectual property management activities

16. Pharmaceutical Industry Best Practices

17. Offering Our Platform to Collaborators Within the University Industry

18. Nanotax® Industry/Academia Collaboration Repurposed Agent for Blood Cancers Academia/Philanthropy/ Industry Collaboration Advancing Innovations to Clinical Proof of Concept Reformulated Chemotherapy Agent Industry/Academia Collaboration SR-13668 Phase 0 Academia/Academia/NCI Collaboration Measurable Outcomes In the Clinic in 2009!