Workshop on Quantitative Pharmacology
and Systems Biology in Pharmaceutical Development
June 18-20, 2014 Dublin City University
Workshop on Quantitative
Pharmacology and Systems
Biology in Pharmaceutical
Development
A workshop examining the background
principles, application, and regulatory
aspects of systems pharmacology methods
in emerging therapeutic developments for
diabetes and cancer.
Location: Dublin City University
Dates:
June 18-20, 2014
http://tinyurl.com/Dublin2014PKPD
With the support of the following organisations
School of Pharmacy and Pharmaceu1cal Sciences Purpose:
Pharmaceuticals form the basis of the majority of treatments in medicine. Pharmacokinetics
(PK - how the body affects the drug) and pharmacodynamics (PD - how the drug affects
the body) are quantitative sciences that represent cornerstones of developing new and
efficacious disease treatments. A rigorous understanding of PK and PD is required by the
drug approval agencies of most nations. The modern approach in the field of PK/PD is
the development of models based on mechanisms of drug action and their alteration of
physiological processes.
This 2.5 day workshop will highlight the principles, techniques, and applications of PK/
PD modelling in drug discovery, development and regulatory approval. Modelling
and simulation allow the optimal design, integration and quantitative interpretation of
pharmacological endpoints that range from molecular biology to human responses and can
greatly expedite the drug development process.
Didactic lectures and recent applications of PK and PD in oncology and metabolic diseases
will be presented by leading experts in the field. At the conclusion of this workshop,
participants from laboratory, clinical, and regulatory environments will be conversant with
relevant quantitative models that are applicable in many aspects of biomedical research
to provide a predictive understanding of pharmacological responses to diverse drugs. The
programme is designed to bring together clinicians, systems biologists, mathematicians,
engineers, drug developers, bioinformatics researchers and regulatory bodies for interactive
discussions focused on their fields.
Day 1 Wednesday June 18th
Intensive Introduction to Pharmacometrics; Applications to Metabolic Diseases
Time
Details
8.00am
Registration opens, Helix Conference Centre, DCU
9.00
Pharmacometrics and Bioinformatics Analysis of Pharmacological Systems I
Clynes, Straubinger, O’Connor
Fáilte and Introduction
9:15-10:10
Prof. William Jusko
SUNY, University at Buffalo
General PK/PD Modelling Perspectives
•
•
•
•
•
Objectives of PK/PD modelling: The field and this workshop
Comparison of key elements of PD versus PK modelling
Basic tenets of PD: Capacity-limitation and turnover/homeostasis
Array of mechanistic PK/PD models
Complexities in PK/PD modelling
10:10-11:00
Prof. Don Mager
SUNY, University at Buffalo
Population PK/PD Modelling
•
•
•
•
•
PK/PD variability
Nonlinear mixed effects modelling
Common inter-subject variability and residual error models
Covariates explaining inter-subject PK/PD variability
Examples of population PK/PD in drug development and therapeutics
Break
Prof. Des Higgins
Professor of Bioinformatics, University College Dublin
Multivariate Analysis of Gene Expression and Proteomics Data Sets
Lunch
• Methods for analysing data from gene expression microaray, RNA-seq or high
throughput proteomics experiments
11:00-11:30
11:30-12:20
12.20-1.30
Drug and Therapy Discovery in diabetes
•
•
•
•
Insulin signalling and glucose transport defects in diabetes
Contraction-mediated glucose disposal
The interaction between glucose transport and gene expression
Mitochondrial function in metabolic regulation
1:30-2:10
Dr. Donal O’Gorman
Director, Centre for Preventive Medicine Dublin City University
Insulin-dependent and –independent regulation of glucose disposal in human skeletal muscle
2:10-2:50
Prof. Jochen Prehn
Professor of Physiology & Director, Centre for Systems Medicine
Royal College of Surgeons in Ireland
Development of computational modelling approaches to understand bioenergetics and
apoptosis signalling at a systems level: towards novel prognostic tools
2:50-3:30
Prof. William Jusko
Modelling Anti-Diabetic Effects
3:30-3:50
Break
3:50-4:40
Prof. Don Mager Modelling Combination Therapy in Diabetes
• Translational modelling of exenatide pharmacokinetics
• Diverse models of pharmacodynamic interactions
• Combination model of metformin and sitagliptin
4:40-5:30
Prof. John Findlay
National University of Ireland-Maynooth
A new therapeutic approach to human insulin resistance and type 2 diabetes
• Retinal binding protein and insulin resistance
• Novel compounds that promote glucose transport
• Understanding the mechanism of action
• New computational modelling approaches to understand the role of glucose
metabolism, mitochondria, and apoptosis signalling
•
•
•
•
Models for glucose – insulin dynamics: minimal to majestic
Diverse mechanisms and models for anti-diabetic drug effects
Target-mediated PK/PD models for vildagliptin
From basic to systems drug/disease models in diabetes
Day 1 Thursday June 19th
Pharmacometrics and Bioinformatics; Applications in Oncology
Time
Details
Pharmacometrics and Bioinformatics Analysis of Pharmacological Systems II
9:00-9:55
Prof.Amin Rostami Professor of systems pharmacology - Manchester Pharmacy School
Physiologically-based PK Modelling in Drug Development
9:55-10:50
Prof. William Jusko
PK/PD Models in Pharmacogenomics
10:50-11:20
Break
11:20-12:15
Dr.Tapesh Santra Systems Biology Ireland - University College Dublin
Predicting cancer subtype specific therapeutic targets by analyzing high-throughput
heterogeneous datasets
12.15-1.30
Lunch
• Applications of “systems biology” approach to prediction of drug absorption,
distribution and elimination
• Extrapolation of in vitro data to predict in vivo pharmacokinetics
• Applications of PBPK in drug development and therapeutics, particularly
endocrinology, drug abuse, and paediatric pharmacology
• Relevance of basic tenets of PK/PD: Capacity-limitation and turnover/homeostasis
• Modelling diverse genomic effects of corticosteroids
• Connecting genomics (PG) and proteomics (PP)
• Circadian rhythms in gene expression in various tissues
• Small systems models for corticosteroid PK/PD/PG/PP
• Mathematical and computational modelling to analyse the network structure of cell
signalling.
• Prediction of responses to perturbations (such as drugs), define the most sensitive
points for interference by drugs, and analyse the specificity of signalling and
adaptation processes.
Drug and Therapy Discovery in Cancer
1:30-2:15
Prof. William Jusko
Chemotherapy PK/PD Models
•
•
•
•
Expectations of irreversible mechanisms
Cell growth and cytotoxicity: profiles and data fitting
Adding complexities: cell cycling, nonlinear cytotoxicity, resistance
Models for tumor growth and inhibition
2:15-3:00
Prof. Robert Straubinger Professor of pharmaceutical sciences - SUNY, University at Buffalo
Modelling Stromal disruption in pancreatic cancer
• Development of computational approaches to understand and overcome sromal
resistance-mediated pancreatic cancer treatment failure
3:00-3:30
Break
3:30-4:15
Dr. Peter O’Gorman
Consultant Haematologist, Mater Misericordiae Dublin
Predicting Drug Response in Patients with Multiple Myeloma
• Individualisation of the selection process for current and emerging therapies for
leukaemia and lymphoma
4:15-5:00
Prof. Don Mager
Translational Systems Pharmacology Modelling of Combinatorial Chemotherapy
• Integrated cell signalling pharmacodynamic model of anti-CD20-based regimens
• Logic-based and dynamical modelling of bortezomib response in U266 cells and
xenografts
Day 3 Friday June 20th
Biologicals; Drug Development, Regulatory Aspects and IndustryApplications
Time
Details
Experimental and Systems Approaches in Biological Drug Development
9:00-9:55
9:55-10:40
Prof, Don Mager PK/PD Modelling of Biological Therapeutics
Prof. Sathy V. Balu-Iyer
SUNY, University at Buffalo
Role of Immunogenicity in Biological Drug Development
• Characteristics and complexities of biological drug absorption and disposition
• Target-mediated drug disposition
• Role of FcRn in monoclonal antibody pharmacokinetics
• Mechanisms of immunogenicity of protein drugs
• Trace protein and antibody aggregates as immunogenic species
• Novel approaches to limiting immunogenicity and inducing tolerance
10:40-11:00
Break
11:00-11:45
Dr. Juan Jose Perez-Ruixo
Role of Quantitative Pharmacology in Biologic Drug Development
• EPO, Peg-EPO, Romiplostim
• Diverse examples of integrated PK/PD models of biological therapeutics, including
oncology and bone disorders
11:45-12:10
Dr. Adrian Dunne
Scientific director and Research Fellow, Model Based Drug Development group,
Janssen Research and Development (Janssen Pharmaceuticals)
• Introduction to population PK/PD, the industry perspective
12:10- 12.40
Dr. An Vermeulen
Senior Scientific director, Johnson and Johnson
• Industrial applications of population PK/PD in drug development
12:40-12.50
Closing Remarks - Martin Clynes (Director NICB)
For nearby hotel accommodation
We suggest the Crowne Plaza Santry: http://tinyurl.com/CPsantry
or Holiday Inn Express, Dublin Airport: http://tinyurl.com/HIsantry
Both are < 4km away
Or accommodation on the DCU campus (http://www.summeraccommodation.dcu.ie/)
We are grateful for support from the following sponsors
Organising committee
Speakers
• Dr. Robert O’Connor, DCU, Senior Programme Leader
Translational Cancer Pharmacology Dublin City University
http://www.nicb.dcu.ie/staff_robert_o_connor.html
• WJ Jusko, PhD, University at Buffalo, State University of New York, SUNY Distinguished Professor
and Chair, Dept. of Pharmaceutical Sciences
http://pharmacy.buffalo.edu/pages/176/Dr.-William-J.-Jusko.html
• Prof. Martin Clynes, DCU, Director, National Inst. for Cellular
Biotechnology Dublin City University
http://www.nicb.dcu.ie/staff_martin_clynes.html
• DE Mager, PharmD, PhD, University at Buffalo, State University of New York, Associate Professor,
Dept. of Pharmaceutical Sciences
http://www.pharmacy.buffalo.edu/pages/183/Dr.-Donald-E.-Mager.html
• Prof. Robert M. Straubinger, University at Buffalo, State
University of New York, Dept. of Pharmaceutical Sciences
http://www.pharmacy.buffalo.edu/pages/183/Dr.-Donald-E.Mager.html
• Prof. Donald E. Mager, PhD, PharmD, University at Buffalo, State
University of New York, Dept. of Pharmaceutical Sciences
http://pharmacy.buffalo.edu/phc/faculty/MAGER.HTML
• Prof. Walter Kolch, UCD Conway, Director, Systems Biology
Ireland
http://www.ucd.ie/sbi/peoplepartners/profiles/walterkolch/
• Prof. Jochen Prehn, Head of Dept and Director Centre for
Human Proteomics and Medical Systems Biology RCSI
Pharmaceutical Sciences
http://www.rcsi.ie/index.jsp?a=1759&n=613
• Dr. Donal O’Gorman, DCU, Director, Centre for Preventive
Medicine, Health and Human Performance
http://www.dcu.ie/info/staff_member.php?id_no=1485
• SV Balu-Iyer, PhD, University at Buffalo, State University of New York, Professor, Dept. of
Pharmaceutical Sciences
http://pharmacy.buffalo.edu/phc/faculty/BALU.HTML
• Dr. Tapesh Santra, UCD Conway, Director, Systems Biology Ireland
http://www.ucd.ie/research/people/systemsbiologyireland/drtapeshsantra/
• Prof. Des Higgins, UCD Conway, Professor of Bioinformatics
http://www.ucd.ie/sbi/peoplepartners/profiles/deshiggins/
• Prof. Jochen Prehn, Head of Dept and Director Centre for Human Proteomics and Medical Systems
Biology RCSI Pharmaceutical Sciences
http://www.rcsi.ie/index.jsp?a=1759&n=613
• Dr. Donal O’Gorman, Director of the Centre for Preventive Medicine (CPM) at Dublin City University
(DCU)
http://www.dcu.ie/info/staff_member.php?id_no=1485
• Dr. Peter O’Gorman Consultant Haematologist, Mater Hospital, Dublin
https://www.materprivate.ie/consultant/dr-peter-o-gorman/
• Dr. Juan Jose Perez-Ruixo Scientific Director at Amgen, Spain
http://www.linkedin.com/profile/view?id=13185877&authType=OUT_OF_NETWORK&auth
Token=IfTN&locale=en_US&srchid=155540931391630659760&srchindex=4&srchtotal=168&trk=vsrp
_people_res_photo&trkInfo=VSRPsearchId%3A155540931391630659760%2CVSRPtargetId%
3A13185877%2CVSRPcmpt%3Aprimary
• Prof. Amin Rostami, Professor of Systems Pharmacology, University of Manchester
http://www.pharmacy.manchester.ac.uk/staff/Amin.Rostami
• Prof. John Findlay, NUI Maynooth
https://www.nuim.ie/people/john-findlay
• Dr. Adrian Dunne, Scientific director and Research Fellow, Model Based Drug Development group,
Janssen Research and Development
• Dr. An Vermeulen, Senior Scientific director, Johnson and Johnson
• Prof. Robert M. Straubinger, University at Buffalo, State University of New York, Dept. of
Pharmaceutical Sciences
http://pharmacy.buffalo.edu/sopps/pages/564/Profile-Directory-Detail.html?ID=193