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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 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. Our Work Is Imperative • Underserved Region » National Cancer Program • Closest NCI Comprehensive Cancer Center is at least 250 miles away NCI Designated Centers • Statewide Access Problem » Limited access to cutting-edge clinical trials in rural populations Cancer Center (24) Comprehensive Cancer Center (39) Planning Grant (6) NCI Progress NCI Designation Differentiators Drug Discovery & Development Office of Therapeutics Discovery & Development Community-based Approach Clinical Trials Office Results More advanced cancer prevention, early detection, treatment, and survivorship 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 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 KUCC Model Basic, Drug Discovery & Translational Research Drug Development & Clinical Research NCI Designation Pathway World-class Cancer Care Education & Outreach 2016 Vision 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 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 Drug Discovery, Delivery & Development 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 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 Drug Discovery, Delivery & Development Reengineered Drug Discovery Process Target -> Chemical Hit 1 Target Selection & Validation 2 Target Production 3 4 High Chemical Throughput Hit Screening Identification Chemical Hit -> Lead 5 6 7 Define Lead Prediction of In vitro Selection PhysioPotency & Criteria Chemical Selectivity Properties In vivo Proof of Concept 8 Early ADMET Lead -> 9 10 11 Pre – In vivo and Prepare for Formulation In vitro IND Screening ADMET Enabling Profiling Activities Enabling Processes A. B. C. D. E. Project prioritization Project management Compound management Process chemistry Communications F. G. H. I. J. Development Candidate Information technology Chemoinformatics Bioinformatics Regulatory strategy IP management Drug Discovery, Delivery & Development 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 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 Drug Discovery, Delivery & Development 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 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 Drug Discovery, Delivery & Development Drug Delivery Center • Planning grant from Kansas Bioscience Authority to establish worldclass 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 DDC Large Molecule Core Competencies 1 Pre-formulation / Characterizations •Empirical phase diagrams •Protein dynamics 2 Screening for stabilizers / additives •HTP •Physical properties 3 Formulation Development / Accelerated Screening • HTP Physical Screening (Temperature, PH, Ionic strength (salt), Protein concentration, Agitation, Freeze / Thaw, Chemical degradation (HPLC-MS) ) 4 Optimization Physical properties of drug substance Drying technologies A) Biophysical characterization, pre-formulation, and formulation of macromolecules (Process steps 1 & 3) Core Competencies B) Stabilization of macromolecules and their complexes C) Solid formulations of biopharmaceuticals using lyophilization/freeze drying D) Adjuvant API formulations for vaccine delivery E) Problem solving - Formulation, delivery and process development F) Novel methodologies for macromolecule characterization 5 Real Time Stability Physical & Biological Properties Drug Discovery, Delivery & Development DDC Small Molecule Core Competencies 1 Lead Optimization 2 Physical/Chemical Characterization • Drugability » In vitro absorption » In vitro metabolism » Protein binding » Early ADME • Solubility • Stability • Crystalline form • Phase-solubility • Polymorphism • Degradation product profile • Water binding isotherms 3 Formulation Development • Solids » Immediate release » Controlled release » Tablets and beads • Liquid » Oral and injectable » Lyophiles 4 Analytical Methods Development 5 Preclinical In-vivo Evaluation • Stability indicating » API » Drug product • Bioanalytical » Analyte in blood, plasma and tissue » Biomarkers • Model » Canine, rodent, primate • Administration route » Parenteral » Non-parenteral • Pharmacokinetics » Clearance, bioavailability A) Formulation of small molecule drugs for preclinical and clinical studies including solid and liquid dosage forms Core Competencies B) Development of novel drug delivery technologies. C) Problem solving in preclinical drug development. D) Physical and chemical characterization of drug molecules. E) Design and synthesis of prodrugs. F) Development of bioanalytical methods. G) Rodent and non-rodent pharmacokinetic and pharmacodynamic studies. DDET 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® 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 DDET 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 Drug Discovery, Delivery & Development Project Management • 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 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 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 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 Drug Discovery, Delivery & Development 23 Drug Discovery, Delivery & Development 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 Final Messages • KU Drug Discovery and Development is a cross-campus, multiinstitutional 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