Drug Discovery, Delivery and Development at the University of Kansas Bringing Pharmaceutical Industry Best Practices

1. Drug Discovery, Delivery and Development at the University of Kansas Bringing Pharmaceutical Industry Best Practices to an Academic Setting Scott Weir, PharmD, PhD Office of Therapeutics, Discovery and Development University of Kansas Cancer Center

2. Our Work Is Imperative Cancer is the #1 killer under the age of 85 12,760 will be diagnosed with cancer in 2007 5,290 will die from cancer in 2007 Kansas’ cancer rates are falling at less than 1/3 of the national average In 2007, cancer rate in Kansas (-0.6) was half national average (-2.1) American Cancer Society. Statistics for 2007.

3. Our Work Is Imperative Underserved Region National Cancer Program Closest NCI Comprehensive Cancer Center is at least 250 miles away Statewide Access Problem Limited access to cutting-edge clinical trials in rural populations Cancer Center (24) Comprehensive Cancer Center (39) Planning Grant (6) NCI Designated Centers

4. NCI Progress NCI Designation Differentiators Drug Discovery & Development Community-based Approach Office of Therapeutics Discovery & Development Clinical Trials Office Results More advanced cancer prevention, early detection, treatment, and survivorship

5. Drug Discovery, Delivery & Development Why are we in this risky business? • Patients • Conduct research which leads to improved disease treatment, prevention and control therapies • Support efforts to establish an NCI designated Comprehensive Cancer Center • Support regional clinical and translational research efforts, i.e., Heartland Institute for Clinical and Translational Research • University • Increase overall research funding • Trains the next generation of drug discovery and development scientists • Create commercial opportunities for the University • Region • Contributes to life sciences and economic growth

6. The Vision Drug Discovery, Delivery and Development • Establish KU as the number one academic institution in advancing anti-cancer agents from discovery to patients • Establish a University-wide, fully integrated organization • Be recognized as a top academic institution in the commercialization of pharmaceutical intellectual property

7. KUCC Model Discover Develop Basic, Drug Discovery & Translational Research Drug Development & Clinical Research 2016Vision NCI Designation Pathway World-classCancer Care Education & Outreach Deliver

8. The Strategy Drug Discovery, Delivery and Development • Balanced drug pipeline • Focus on novel therapies and targets • Improved delivery of marketed drugs • Alignment with KU Translational Research priorities • NCI designation of University of Kansas Cancer Center • Heartland Institute for Clinical and Translational Research • Leverage internal and external (outsourcing) expertise • Bring pharmaceutical industry best practices to KU • High performance project teams • “Pharma” drug profiling • Partnering with industry and other academic institutions

9. Drug Discovery, Delivery & Development KU Strengths • #4 School of Pharmacy (based on total NIH funding, #1 based on NIH funding per faculty FTE) • Established KU cores and centers • University priority and commitment • Stowers Institute for Medical Research • Ewing Kauffman Foundation • Wealth of drug development resources in the region • Life sciences growth in the region • Focus on collaboration with academic, non-profit and industry partners

10. Management Oversight of the Program Scott J. Weir, PharmD, PhD Director, Office of Therapeutics Discovery & Development 20 years at Marion Laboratories, MMD, HMR, Aventis, Quintiles and Aptuit Expertise in advancing compounds from discovery to clinical proof of concept Management of drug discovery, delivery and development Drug Discovery, Delivery & Development G. Sitta Sittampalam, PhD • Deputy Director, Office of Therapeutics, Discovery and Development • 23 years at Eli Lilly & Company • High throughput screening and lead optimization expertise • Oversight of biology and chemistry interface

11. Drug Discovery, Delivery & Development

12. Drug Discovery, Delivery & Development Reengineered Drug Discovery Process DevelopmentCandidate Target -> Chemical Hit Chemical Hit -> Lead Lead -> 1 Target Selection & Validation 2 Target Production 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 • Information technology • Chemoinformatics • Bioinformatics • Regulatory strategy • IP management Enabling Processes • Project prioritization • Project management • Compound management • Process chemistry • Communications

13. Drug Discovery Leadership Barbara N. Timmermann, PhD Chair, Department of Medicinal Chemistry and University Distinguished Professor 27 years experience in natural products chemistry Principal Investigator, Center for Cancer Experimental Therapeutics Leadership role in reengineering KU Drug Discovery Drug Discovery, Delivery & Development Jeffrey Aube', PhD • Professor of Medicinal Chemistry • Director, Chemical Methodology and Library Design Center of Excellence • 24 years experience in medicinal chemistry • Directing chemistry support laboratory for KU Drug Discovery program

14. Drug Discovery Leadership G. Sitta Sittampalam, PhD Deputy Director, Office of Therapeutics, Discovery and Development 23 years at Eli Lilly & Company High throughput screening and lead optimization expertise Oversight of biology and chemistry interface Drug Discovery, Delivery & Development Rathnam Chaguturu, PhD • Director, High Throughput Screening Lab • 24 years industry experience in drug discovery at FMC Corporation and Sierra Biosciences • Pioneer of high throughput screening technology

15. Drug Delivery Center Planning grant from Kansas Bioscience Authority to establish world-class innovation center Builds on KU’s strong history in drug delivery Managed as an industry unit by pharma experts Collaborations with Universities Industry Venture Capital Federal Funding Sources State Economic Development Organizations Foundations and Societies Current plan to grow drug delivery research and service work from currently ~$4.5M to ~$15M annually Drug Discovery, Delivery & Development

16. DDC Large Molecule Core Competencies Drug Discovery, Delivery & Development A) Biophysical characterization, pre-formulation, and formulation of macromolecules (Process steps 1 & 3) B) Stabilization of macromolecules and their complexes C) Solid formulations of biopharmaceuticals using lyophilization/freeze drying D) Adjuvant API formulations for vaccine delivery Core Competencies E) Problem solving - Formulation, delivery and process development F) Novel methodologies for macromolecule characterization

17. Drug Discovery, Delivery & Development DDC Small Molecule Core Competencies A) Formulation of small molecule drugs for preclinical and clinical studies including solid and liquid dosage forms B) Development of novel drug delivery technologies. C) Problem solving in preclinical drug development. D) Physical and chemical characterization of drug molecules. Core Competencies E) Design and synthesis of prodrugs. F) Development of bioanalytical methods. G) Rodent and non-rodent pharmacokinetic and pharmacodynamic studies.

18. Drug Delivery Leadership Valentino Stella, PhD Distinguished Professor, Pharmaceutical Chemistry Principle Investigator, NCI Contract, Development of Dosage Forms and Delivery Systems for Antitumor Agents Formulated Taxol®, Velcade®, pentostatin Pro-drugs Development of Captisol® DDET Roger A. Rajewski, PhD • Director, Biotechnology Innovation and Optimization Center • 18 years industrial and academic experience • Pro-drugs • Development of Captisol® • Leadership role in reengineering KU Drug Discovery

19. Drug Delivery Leadership Charles (Russ) Middaugh, PhD Higuchi Distinguished Professor, Pharmaceutical Chemistry Laboratory for Macromolecular and Vaccine Stabilization Protein folding and stabilization Formulation and delivery of peptides, proteins, nucleic acids, viruses and bacteria as pharmaceutical agents Pharmaceutical industry experience DDET

20. High performance project teams Led by project managers with pharma and CRO experience Project planning Objectives Go/no go decision points Decision criteria Completely integrated with IP management activities Integrated plans including studies conducted with industry partners Pharma “profiling” aids to best position IP for licensing Drug Discovery, Delivery & Development Project Management

21. Project Management Melinda Broward, BSc, MSc Project Director, Office of Therapeutics, Discovery and Development 19 years pharmaceutical industry experience Expertise in preclinical drug safety (toxicology and safety pharmacology), early ADME and high throughput screening Drug Discovery, Delivery & Development Michael B. Hughes, BSc, MBA • Project Director, Office of Therapeutics, Discovery and Development • 14 years pharmaceutical industry experience • Expertise in analytical chemistry, pharmaceutics and project management

22. Drug Discovery, Delivery & Development Collaboration • Stowers Institute for Medical Research • Kansas Bioscience Authority • Kansas Technology Enterprise Corporation • Children’s Mercy Hospital • OncImmune Inc. • Mayo Clinic Comprehensive Cancer Center • Scripps Research Institute • Beckloff Associates • Cerner Corporation • Universities • Local Start-Up Companies • Contract Drug Development Organizations • Non-profit foundations and societies

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24. Funding Sources R&D Infrastructure NIH and NCI funded centers and cores KTEC Biotechnology Innovation and Optimization Center Kansas Bioscience Authority KU Endowment Federally funded projects Reproductive Biology Center of Excellence Alzheimer’s Disease Partnering Supporting existing local companies and future start-ups Licensing technology to pharma Translational research focused foundations and societies Drug Discovery, Delivery & Development

25. Drug Discovery, Delivery & Development Final Messages • KU Drug Discovery and Development is a cross-campus, multi-institutional program • Success is being driven by • Applying industry best practices to university • Creating an integrated, efficient drug discovery and development organization • Establishing high performance, highly collaborative project teams through effective planning and management • Leveraging relationships with other institutions and industry partners to advance projects and strengthen our program • KU Drug Discovery and Development plays a key role in establishing an NCI designated comprehensive cancer center at the University of Kansas