drug discovery, delivery and development at the university of kansas bringing pharmaceutical...

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


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


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 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 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 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


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


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 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


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


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


23


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


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 and development at the university of kansas bringing pharmaceutical...

Documents

imperative cancer

delivery development

generation of drug discovery

kansas cancer rates

advanced cancer prevention

anticancer agents

american cancer society

development scientists