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Drug Discovery, Delivery Drug Discovery, Delivery and Development and Development
at the University of Kansas at the University of Kansas
Bringing Pharmaceutical Industry Best Bringing Pharmaceutical Industry Best Practices to an Academic SettingPractices to an Academic Setting
Scott Weir, PharmD, PhDScott Weir, PharmD, PhDOffice of Therapeutics, Discovery and DevelopmentOffice of Therapeutics, Discovery and Development
University of Kansas Cancer CenterUniversity of Kansas Cancer Center
Our Work Is ImperativeOur 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 ImperativeOur 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
NCI Designated Centers
Cancer Center (24)Comprehensive Cancer Center (39)
Planning Grant (6)
More advanced cancer prevention, early detection, treatment, and survivorship
Drug Discovery & Development
Community-based Approach
Office of Therapeutics Discovery & Development
Results
ClinicalTrials Office
NCI Designation Differentiators
NCI ProgressNCI Progress
• 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
Why are we in this risky business?Why are we in this risky business?
Drug Discovery, Delivery & DevelopmentDrug Discovery, Delivery & 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
Drug Discovery, Delivery and DevelopmentDrug Discovery, Delivery and Development
The VisionThe Vision
2016Vision
2016Vision
Basic, Drug Discovery & Translational
Research
Basic, Drug Discovery & Translational
Research
Drug Development
& Clinical Research
Drug Development
& Clinical Research
Education & Outreach
Education & Outreach
World-classCancer Care
World-classCancer Care
NCI Designation Pathway
KUCC ModelKUCC Model
Drug Discovery, Delivery and DevelopmentDrug 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
The StrategyThe Strategy
KU StrengthsKU 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 & DevelopmentDrug Discovery, Delivery & Development
Management Oversight of the ProgramManagement 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 & DevelopmentDrug Discovery, Delivery & Development
Reengineered Drug Discovery Process
1Target
Selection &
Validation
2
Target Production
3High
ThroughputScreening
4Chemical
HitIdentification
Target -> Chemical Hit Chemical Hit -> Lead
5Define Lead
SelectionCriteria
6Prediction of
Physio-ChemicalProperties
7In vitro
Potency & Selectivity
In vivo Proof
of Concept
8Early
ADMET
Lead ->
9Pre –
FormulationScreening
10In vivo and
In vitro ADMETProfiling
11Prepare for
IND EnablingActivities
DevelopmentCandidate
Enabling ProcessesA. Project prioritizationB. Project managementC. Compound managementD. Process chemistryE. Communications
F. Information technologyG. ChemoinformaticsH. BioinformaticsI. Regulatory strategyJ. IP management
Drug Discovery, Delivery & DevelopmentDrug Discovery, Delivery & Development
Drug Discovery LeadershipDrug 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 & DevelopmentDrug Discovery, Delivery & Development
Drug Discovery LeadershipDrug Discovery LeadershipG. 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 & DevelopmentDrug Discovery, Delivery & Development
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 & DevelopmentDrug Discovery, Delivery & Development
DDC Large Molecule Core CompetenciesDDC Large Molecule Core Competencies1
Pre-formulation / Characterizations
2 Screening for stabilizers / additives
3 Formulation Development /
Accelerated Screening
4 Optimization
5 Real Time Stability
•Empirical phase diagrams•Protein dynamics
•HTP•Physical properties
• HTP Physical Screening(Temperature, PH, Ionic strength (salt),
Protein concentration, Agitation, Freeze / Thaw, Chemical degradation
(HPLC-MS) )
Physical properties of drug substanceDrying technologies
Physical & Biological Properties
A) Biophysical characterization, pre-formulation, and formulation of macromolecules (Process steps 1 & 3)
C) Solid formulations of biopharmaceuticals using lyophilization/freeze drying
B) Stabilization of macromolecules and their complexes
D) Adjuvant API formulations for vaccine delivery
E) Problem solving - Formulation, delivery and process development
F) Novel methodologies for macromolecule characterization
Cor
e C
ompe
tenc
ies
Drug Discovery, Delivery & DevelopmentDrug Discovery, Delivery & Development
DDC Small Molecule Core CompetenciesDDC Small Molecule Core Competencies1
Lead Optimization2
Physical/ChemicalCharacterization
3Formulation
Development
4 Analytical Methods
Development
5 Preclinical
In-vivo Evaluation
• Drugability» In vitro absorption» In vitro metabolism» Protein binding» Early ADME
• Solubility• Stability• Crystalline form• Phase-solubility • Polymorphism• Degradation product profile• Water binding isotherms
• Solids» Immediate release» Controlled release» Tablets and beads
• Liquid» Oral and injectable» Lyophiles
• 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
Cor
e C
ompe
tenc
ies
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.
Drug Discovery, Delivery & DevelopmentDrug Discovery, Delivery & Development
Drug Delivery LeadershipDrug Delivery Leadership
DDET
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
Drug Delivery LeadershipDrug Delivery Leadership
DDET
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
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 & DevelopmentDrug Discovery, Delivery & Development
Project ManagementProject 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 & DevelopmentDrug Discovery, Delivery & Development
CollaborationCollaboration• 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 & DevelopmentDrug Discovery, Delivery & Development
Funding SourcesFunding 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 & DevelopmentDrug Discovery, Delivery & Development
Final MessagesFinal 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
Drug Discovery, Delivery & DevelopmentDrug Discovery, Delivery & Development