13th European ISSX Meeting Registration Brochure

13TH EUROPEAN

ISSX MEETING

University of Strathclyde | Glasgow, Scotland June 22-25, 2015

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JOIN US AT THE 13TH EUROPEAN ISSX MEETING Dear colleagues and friends, On behalf of the International Society for the Study of Xenobiotics (ISSX), you are warmly invited to join us at the 13th European ISSX Meeting which convenes June 22 - 25, 2015 at the University of Strathclyde’s Technology and Innovation Centre in Glasgow, Scotland.

The Meeting Organising Committee has carefully designed the programme to address key research topics including: PBPK Modelling, Stem Cell Technology Developments and their Application to Drug Metabolism and Drug Safety, the Role of Drug Transporters, Epigenomics in Drug Metabolism and Disease, Mass Spectrometry of Small Molecules, and much more. The meeting additionally will feature a wide range of contemporary research topics in the form of poster presentations as well as industry-sponsored educational sessions each morning prior to the general meeting. Complementing the meeting, top suppliers to the scientific community will present their products and services during the meeting exhibition.

The Meeting Organising Committee is particularly keen to encourage new investigators to use this meeting as a platform

to communicate their own research and to further their career progression. New investigators will meet leading researchers while learning, networking, and socialising with other delegates in a friendly yet stimulating environment. Discounted registration fees are available for ISSX members as well as pre- and postdoctoral students. Please visit the meeting web site at www.issx.org/Glasgow for information.

Attendees of the 13th European ISSX Meeting can experience first-hand the charming and vibrant city of Glasgow. There is a diverse array of cultural and entertainment options available along with an excellent dining scene. Supported by a great transportation network, meeting attendees and accompanying guests can take in all that this unique and beautiful city has to offer.

We are looking forward to welcoming you in Glasgow for an exciting and educational meeting!

Sincerely, C.R. Wolf, Ph.D., OBE Ann Daly, Ph.D. University of Newcastle Dundee University Meeting Co-Chairs

MEETING ORGANISING COMMITTEE CO-CHAIRS: Roland Wolf University of Dundee, Dundee, Scotland

Ann Daly Newcastle University, Newcastle upon Tyne, England

MEETING ORGANISING COMMITTEE:

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John Hayes University of Dundee, Dundee, Scotland

Colin Suckling University of Strathclyde, Glasgow, Scotland

Brian Houston University of Manchester, Manchester, England

Geoff Tucker University of Sheffield, Sheffield, England

Neil Kitteringham University of Liverpool, Liverpool, England

Michael Voice Cypex, Ltd., Dundee, Scotland

Michael McMahon University of Dundee, Dundee, Scotland

Heather Wallace University of Aberdeen, Aberdeen, Scotland

Richard Meehan University of Edinburgh, Edinburgh, Scotland

Matt Wright Newcastle University, Newcastle upon Tyne, England

Munir Pirmohamed University of Liverpool, Liverpool, England

SHORT COURSE DESCRIPTIONS SHORT COURSE 1: MASS SPECTROMETRY IN DRUG METABOLISM STUDIES Chairs: Neil Kitteringham, University of Liverpool, Liverpool, UK and Ian Wilson, Imperial College, London, UK Early determination of metabolic stability and metabolic fate of compounds in drug discovery is seen as a key part of ensuring that compounds are only selected for further studies if they have properties that make them suitable for future development. The use of LC-MS is now ubiquitous by discovery teams to determine the pharmackokinetics, metabolic stability and the metabolic fate of drug candidates. This short course will illustrate how LC-MS is used to detect and identify metabolites, highlight metabolic “hot spots,” identify compounds with reactive metabolite liabilities, and enable structure optimization.

Short Course 2: Stem Cell Derived Tissues in Toxicology Chairs: Chris Goldring, University of Liverpool, Liverpool, UK and Matt Wright, Newcastle University, Newcastle upon Tyne, UK Current preclinical drug testing does not predict some forms of adverse drug reactions in humans. Adhering to the principles of the 3Rs, efforts at improving predictability of drug-induced tissue injury in man have included using stem cell technology to generate human cells for screening for adverse effects of drugs in man. This short course will explain the background to this area, why stem cells may be useful tools in the assessment tool-box to predict basic cellular perturbation, what we need from the cells, how to compare them with their terminally-differentiated human counterparts and what techniques are used to carry out this phenotyping. Real-world examples of how cells differentiated from stem cells are being deployed to investigate drug/chemical toxicity will be described. Four senior researchers in this field will present a background, and the following organ systems will be discussed in detail: liver, heart, and kidney.

Short Course 3: Physiologically Based Pharmacokinetic Modelling Chairs: Geoff Tucker, Simcyp Limited, Sheffield, UK and Brian Houston, University of Manchester, Manchester, UK The application of physiologically based pharmacokinetic (PBPK) modelling has come of age in drug development and regulation, reflecting significant advances over the past 20 years in the predictability of key pharmacokinetic parameters from human in vitro data, especially with respect to drug-drug interactions, and the availability of dedicated software platforms and associated data bases. This course will provide an understanding of the basic principles of in vitro – in vivo extrapolation; key issues will be illustrated with specific case studies, and the special considerations necessary to extend PBPK modelling to predict paediatric drug doses will be explained. The current status of regulatory acceptance of simulations based on PBPK modelling will be discussed.

Short Course 4: New Horizons in Mass Spectrometry Chairs: Andy Pitt, Aston University, Birmingham, UK and Neil Kitteringham, University of Liverpool, Liverpool, UK This short course aims to provide an overview of the exciting, new, and innovative applications for mass spectrometry in the study of xenobiotics and their interactions with proteins.

The interface between small molecules and biological macromolecules is at the heart of both drug efficacy and xenobiotic toxicity—mass spectrometry offers the perfect platform to explore this interface. The first three talks explore different approaches to deploy mass spectrometry within this context, whilst the final talk addresses the thorny issue of dealing with large data sets from both metabolomics and proteomic studies.

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SCIENTIFIC PROGRAM

AS OF JANUARY 2, 2015

SHORT COURSES SHORT COURSE 1: Mass Spectrometry in Drug Metabolism Studies Chairs: Ian Wilson, Imperial College, London, United Kingdom and Neil Kitteringham, University of Liverpool, Liverpool, United Kingdom LC-MS in Metabolite Identification in High Throughput Drug Discovery Anthony Dickie, Evotec (UK) Ltd., Abingdon, United Kingdom Detecting and Identifying Reactive Metabolites Sara Amberntsson, AstraZeneca, Molndal, Sweden The Use of LC-MS for Comprehensive Metabolite Characterisation and Identification Russell Mortishire-Smith Waters, Wilmslow, United Kingdom Tips, Tricks and LC-ICPMS for Metabolite Detection and Identification Ian Wilson, Imperial College, London, United Kingdom SHORT COURSE 2: Stem Cell Derived Tissues in Toxicology Chairs: Chris Goldring, University of Liverpool, Liverpool, United Kingdom and Matt Wright, Newcastle University, Newcastle upon Tyne, United Kingdom The Application of Stem Cells in Toxicology: What do We Need and Why do We Need Them?

Chris Goldring, University of Liverpool, Liverpool, United Kingdom Derivation of Cardiomycytes, Stem Cells, and Toxicity Testing Chris Denning, University of Nottingham, Nottingham, United Kingdom

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Stem Cell-Derived Renal Cells Daniele Zink, Institute of Bioengineering and Nanotechnology, Singapore

Hepatocyte Stem Cells in Toxicity Testing Matt Wright, Newcastle University, Newcastle upon Tyne, United Kingdom SHORT COURSE 3: Physiologically Based Pharmacokinetic Modelling Chairs: Geoff Tucker, Simcyp Limited, Sheffield, United Kingdom and Brian Houston, University of Manchester, Manchester, United Kingdom Principles of IVIVE Michael Gertz, Roche, Basel, Switzerland PBPK Case Studies Karen Rowland-Yeo, Simcyp Limited, Sheffield, United Kingdom Paediatric PBPK Modelling Kay Ogunbero, University of Manchester, Manchester, United Kingdom A European Regulatory Perspective on PBPK Modelling Terry Shepard, Medicines and Healthcare Products Regulatory Agency (MHRA), Slough, United Kingdom SHORT COURSE 4: New Horizons in Mass Spectrometry Chairs: Andy Pitt, Aston University, Birmingham, United Kingdom and Neil Kitteringham, University of Liverpool, Liverpool, United Kingdom New Applications of Proteomics in Biomedical Research Andy Pitt, Aston University, Birmingham, United Kingdom Imaging for Xenobiotics and Metabolites Malcolm Clench, Sheffield Hallam Uniersity, Sheffield, United Kingdom

Data Independent Acquisition: A New Era for Quantitative Proteomics?

Roz Jenkins, University of Liverpool, Liverpool, United Kingdom Making Sense of the Data: How to Handle Large Proteomic and Metabolomics Datasets Karl Burgess, University of Glasgow, Glasgow, United Kingdom

SYMPOSIA KEYNOTE ADDRESS: Protein Kinases as Drug Targets Chair: Roland Wolf, University of Dundee, Dundee, United Kingdom Speaker: Professor Sir Philip Cohen, University of Dundee, Dundee, United Kingdom SYMPOSIUM 1: Recent Developments in Stem Cell Technology and its Application to Drug Metabolism and Drug Safety Testing Chairs: David Hay, University of Edinburgh, Edinburgh, United Kingdom and Ludovic Vallier, University of Cambridge, Cambridge, United Kingdom Pluripotent Stem Cell Hepatocytes and Tissue Engineering David Hay, University of Edinburgh, Edinburgh, United Kingdom Pluripotent Stem Cell Hepatocytes and Cholangiocyte Models Ludovic Vallier, University of Cambridge, Cambridge, United Kingdom Animal Models Stephen Strom, Karolinska Institute, Stockholm, Sweden

SYMPOSIUM 2: Expanding the Boundaries of PKPD Modelling Chairs: Geoff Tucker, Simcyp Limited, Sheffield, United Kingdom and Brian Houston, University of Manchester, Manchester, United Kingdom Systems Pharmacology Meindert Danhof, Leiden University, Leiden, Netherlands Modelling in Toxicity Tarjinder Sahota, GlaxoSmithKline, Uxbridge, United Kingdom Incorporating Transporter Kinetics into PBPK Models Alexandra Galetin, University of Manchester, Manchester, United Kingdom PBPK Modelling of mABs Linzhong Li, Simcyp Limited, Sheffield, United Kingdom SYMPOSIUM 3: Systems Toxicology Chairs: Paul Watkins, The Hamner Institues for Health Sciences, Research Triangle Park, NC, United States and Bob van de Water, Leiden University, Leiden, Netherlands Systems Microscopy to Unravel the Wiring of Toxicity Pathways in Druginduced Liver Injury Bob van de Water, Leiden University, Leiden, Netherlands A Quantitative Systems Biology Analysis of Signal Transduction Networks Underlying DILI Ursula Klingm端ller, DKFZ, Heidelberg, Germany Systems Modelling Approaches to Predict Idiosyncratic DILI Paul Watkins, The Hamner Institues for Health Sciences, Research Triangle Park, NC, United States Integration of QSAR and PK-PD Modelling in Cardiac Drug Safety Assessment Sebastian Polak, Simcyp Limited, Sheffield, United Kingdom

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SYMPOSIUM 4: Clinical Implementation of Pharmacogenomics Chairs: Ann Daly, Newcastle University, Newcastle upon Tyne, United Kingdom and Matthias Schwab, Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany Implementation of Pharmacogenomics in Clinical Practice-focus on Evidencebased Medicine and Cost-effectiveness Munir Pirmohamed, University of Liverpool, Liverpool, United Kingdom Importance of Drug Transporter Polymorphisms and Scope for Clinical Implementation Matthias Schwab, Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany Pharmacogenomic Approaches to Treatment of Cystic Fibrosis Margareta Amaral, University of Lisboa, Lisbon, Portugal HLA Genotype and Risk of Adverse Drug Reaction: Prospects for Clinical Implementation Duncan McHale, UCB Pharma, Stockport, United Kingdom SYMPOSIUM 5: Role of Drug Transporters: Current and Future Perspectives (an ITC Sponsored Symposium) Chairs: Donald Tweedie, Boehringer Ingelheim, Ridgefield, CT, United States and Brian Houston, University of Manchester, Manchester, United Kingdom Regulatory View Eva Gil Berglund, Medical Products Agency, Uppsala, Sweden N1-methylnicotinamide: An Endogenous Probe for Drug Interactions by Renal Cation Transporters?

Martin Fromm, University of ErlangenNuremberg, Erlangen, Germany

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Predictions of Cellular Drug Binding and Implications for Intracellular Drug Concentrations and Effects Par Matsson, Uppsala University, Uppsala, Sweden Substrate/Inhibition Assays and Prediction of DDIs Christoph Funk, F. Hoffmann-La Roche Ltd., Basel, Switzerland SYMPOSIUM 6: Advances in Pathways of Chemically-induced Oxidative Stress and DNA Damage Chairs: John Hayes and Ken Tew Control of Redox Homeostasis by the Nrf2 Regulatory Network John Hayes, University of Dundee, Dundee, United Kingdom Regulation of Protein Function by Glutathionylation During Oxidative Stress Kenneth Tew, Medical University of South Carolina, Charleston, SC, United States The Redox Chemistry of Antioxidants Claus Jacob, Saarland University, Saarland, Germany Control of H2O2 Transport in and Between Cells Roberto Sitia, San Raffaele Scientific Institute, Milan, Italy SYMPOSIUM 7: Humanised Animal Models in Drug Development Chairs: Colin Henderson, University of Dundee, Dundee, United Kingdom and Frank Gonzalez, National Cancer Institute, Bethesda, MD, United States Humanised Mouse Models of Drug Metabolism Colin Henderson, University of Dundee, Dundee, United Kingdom Mouse Models for Elucidation of CYP2D6 and CYP2C19 Function in the Developing and Adult Brain Magnus Ingelman-Sundberg, Karolinska Institute, Stockholm, Sweden

Knockout and Humanised Mouse Models for Detoxifying Proteins Alfred Schinkel, The Netherlands Cancer Institute, Amsterdam, Netherlands

Genetic-Epigenetic Interactions and Implications for Genome Stability/ Function Thomas Carell, Ludwig-Maximilians University, Munich, Germany

Lipoprotein and Bile Acid Profiles in FRG Mice with Humanised Livers Ewa Elis, Karolinska Institute, Stockholm, Sweden

Spatial Organisation of the Nucleus and Influence on Human Disease Wendy Bickmore, Institute of Genetics and Molecular Medicine, Edinburgh, United Kingdom

SYMPOSIUM 8: The Contribution of the Gut Microbiome to Drug Metabolism, Drug Interactions and Drug Toxicity Chairs: Heather Wallace, University of Aberdeen, Aberdeen, United Kingdom and Elaine Holmes, Imperial College London, London, United Kingdom Microbiome Metabolomics Elaine Holmes, Imperial College London, London, United Kingdom Impact of Host-microbial Interactions on Toxicokinetics of Tacrine Eric Chan, National University of Singapore, Singapore Lecture Title Pending Sven Pettersson, Karolinska Institute, Stockholm, Sweden Diet-microbiome Interactions Bernard Corfe, University of Sheffield, Sheffield, United Kingdom SYMPOSIUM 9: Epigenomics in Drug Metabolism and Disease Chairs: Richard Meehan, Institute of Genetics and Molecular Medicine, Edinburgh, United Kingdom and Jonathan Moggs, Novartis, Basel, Switzerland Epigenomics: Impact for Translational Sciences Jonathan Moggs, Novartis, Basel, Switzerland 5hmC – Tissue Specificity and Modulation by Xenobiotics John Thomson, Institute of Genetics and Molecular Medicine, Edinburgh, United Kingdom

SYMPOSIUM 10: Proteins as Targets for Covalent Modification by Xenobiotics: Therapeutic Opportunities versus Toxicological Risk Chairs: Thomas Baillie, University of Washington, Seattle, WA, United States and Kevin Park, University of Liverpool, Liverpool, United Kingdom Pharmacological, Physiological, and Pathological Consequences of Drug Bioactivation and Covalent Binding Kevin Park, University of Liverpool, Liverpool, United Kingdom Reactive Drug Metabolites and Targeted Covalent Inhibitors: A RiskBenefit Perspective Thomas Baillie, University of Washington, Seattle, WA, United States Challenges in Developing AZD9291 – An Irreversible Inhibitor of EGFR-TKI Sensitising and Resistant Mutations in Non-small Cell Lung Cancer Peter Ballard, AstraZeneca, Cheshire, United Kingdom Inhibitors of Cathepsin C: Not Your Typical Oral Small Molecules Michael Palovich, GlaxoSmithKline, Uxbridge, United Kingdom

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SYMPOSIUM 11: Predicting Human Responses During Drug Discovery and Development Chairs: Roland Wolf, University of Dundee, Dundee, United Kingdom and Peter Moldeus, Karolinska Institute, Stockholm, Sweden Application of in vivo Reporters for Stress Responses in Drug Development Roland Wolf, University of Dundee, Dundee, United Kingdom In vitro Approaches to Toxicity Testing Ruth Roberts, AstraZeneca, Stockport, United Kingdom Establishing Potential Safety Liabilities in Early Drug Development Bill Pennie, Takeda, Norwich, CT, United States The Application of Epigenome and Kinome-based Bioassays for Risk Assessment Ivonne Rietjens, Wageningen University, Wageningen, Netherlands SYMPOSIUM 12: Conjugating Enzymes and Hydrolases in Endogenous and Foreign Compound Metabolism Chairs: Michael Arand, University of Zurich, Zurich, Switzerland and John Miners, Flinders University, Adelaide, Australia Microsomal (and Soluable) Epoxide Hydrolase in Eicosanoid Metabolism and its Physiological Consequences Anne Marowsky, University of Zurich, Zurich, Switzerland DDIs Involving Glucuronidated Drugs John Miners, Flinders University, Adelaide, Australia Role of SULTs in Metabolic Activation Hansruedi Glatt, German Institute of Human Nutrition, Potsdam, Germany

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Carboxylesterase 1 – Substrates, Regulation of Enzyme Activity and Pharmacogenetics Henrik Rasmussen, Region Hovedstadens Psykiatri, Copenhagen, Denmark

PLENARY SESSION: Inflammation: Effects on Drug Metabolism and Disease Aetiology Chairs: Kathie Knights, Flinders University, Adelaide, Australia and Eddie Morgan, Emory University, Atlanta, GA, United States Regulation of Drug Transporters in Inflammation: Impact on Drug Disposition Micheline Piquette-Miller, University of Toronto, Toronto, Canada Inflammatory Regulation of Human Drug Metabolising Enzymes Ulrich Zanger, Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany Role of NO in Inflammatory Regulation of Drug Metabolising Enzymes Edward T. Morgan, Emory University, Atlanta, GA United States Inflammation and Liver Disease Percy Knolle, Technische Universität München, Munich, Germany SPECIAL KEYNOTE CLOSING LECTURE Chairs: Roland Wolf, University of Dundee, Dundee, United Kingdom and Ann Daly, Newcastle University, Newcastle upon Tyne, United Kingdom Speaker: Frank Gonzalez, National Cancer Institute, Bethesda, MD, United States

REGISTRATION INFORMATION The meeting registration fee includes admittance to: • Scientific Symposia and Special Lectures • Awards Presentation and Lectures • Poster Presentations • Poster Awards Competition Review and Awards Session • Exhibition • Civic Reception • Opening Welcome Reception The short courses are separately ticketed offerings and may be added to a registration at an additional fee.

REGISTRATION FEES

SHORT COURSES

All Prices in US Dollars Early

Regular On-Site

January 1—March 20

March 21—June 21

June 22—25

ISSX Member

$175

$225

$250

Nonmember

$225

$275 $325

Student Member

$100

$125

$150

Student Non-Member

$125

$150

$175

MEETING REGISTRATION

Early

Regular On-Site

January 1—March 20

March 21—June 21

June 22—25

ISSX Member

$615

$715

$795

Nonmember

$775

$845 $955

Student Member

$250

$275

$300

Student Non-Member

$275

$300

$325

Guest $50 $50 $50

PLEASE NOTE: The meeting registration fee does not include access to the short courses nor the ISSX social event at the Old Fruit Market. Guest registration includes a meeting tote bag and admission to the opening welcome reception, Civic Reception, and all refreshment breaks. Guest registration does not include admittance to the scientific sessions or the ISSX social event at the Old Fruit Market. Tickets to the social event may be purchased for guests in advance.

MEETING CANCELLATION POLICY Registration fees for the meeting and for short courses, less an administrative processing fee of $100 USD, will be refunded if a written/emailed request is received on or before Monday, June 1, 2015. No refunds can be issued past this date as ISSX is required to provide guarantees and pay deposits for various meeting services based on anticipated attendance. Thank you for your understanding.

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SOCIAL PROGRAM Opening Welcome Reception

Meeting Dinner and Ceilidh

Start the meeting at the Opening Welcome Reception in the exhibition and poster area of the Technology and Innovation Centre on Monday, June 22.

Enjoy hors d’oeuvres and drinks while you meet with our meeting exhibitors and fellow attendees.

Join us at the premier social event of the meeting at the Old Fruit Market of Glasgow which has kept all of its period charm, including its lofty vaulted roof, cast iron columns, balcony, and slender Victorian architecture. Attendees will enjoy a delicious buffet dinner, drinks, and a ceilidh.

Included with full meeting registration and guest ticket purchase.

Civic Reception The Glasgow City Council would like to welcome ISSX to Glasgow with a Civic Reception on Tuesday, June 23 at 18:30. This unique event will be held in the prestigious surroundings of the City Chambers in the Picture Gallery. The Lord Provosts of the City will be in attendance to greet delegates and welcome you to Glasgow. The City Chambers is in the very heart of Glasgow and is one of the city’s most important and prestigious buildings. A grand and imposing edifice overlooking George Square, the City Chambers is an impressive symbol of Glasgow’s political strength and historical wealth.

Completed in 1888, the City Chambers has for over 100 years been the headquarters of successive councils serving the City of Glasgow.

Complimentary - Advanced registration required.

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The word ceilidh (kay-lee) descended from the Gaelic word for “gathering” or “party”… However, these days when people think of a ceilidh, they think of a fun filled night of dancing, good music, and great company! The beauty of a ceilidh is that everyone can take part. You will be walked through the steps under the watchful eye of the professional caller who will be with you every step of the way – walking you through the moves before each dance and continuing to call out helpful hints throughout the rest of the dances. It is sure to be a wonderful time.

Make plans to join us at the Old Fruit Market on Wednesday, June 24.

Separate registration fee applies.

GENERAL INFORMATION Meeting Location

Climate/Time Zone

University of Strathclyde Technology and Innovation Centre 121 George Street Glasgow, Scotland G1 1RD

The month of June is characterized by gradually rising daily high temperatures, with daily highs around 17° C (63°F) throughout the month, sometimes exceeding 23° C (73°F). The daily low temperature ranges from 8° C (47°F) to 11° C (51°F).

Accommodations ISSX has arranged for special rates at several hotels in different price categories in the area near the Technology and Innovation Centre in Glasgow. The hotels are within walking distance to the meeting facility.

Attendees are welcome to secure lodging at alternative venues.

Reservations for hotels in our housing block will be accepted on a first-come, first-served basis. A limited number of hotel rooms are available at each property. Reservations will be accepted based upon availability up to two weeks before our meeting convenes. It is to the attendee’s advantage to reserve their hotel accommodations as soon as possible.

Glasgow is located in the Greenwich Mean Time zone and Daylight Savings Time will be observed at the time of the meeting.

Exhibit Hall Top suppliers will be on hand to share the latest products and services to help you advance your research. Bring plenty of business cards.

Language The official language of the 13th European Meeting is English. All abstracts and presentations will be in English. No simultaneous translation will be available.

Reserve lodging via this web site: www.issx.org/13euro/hotel

Awards Program Nominations are currently being accepted for the scientific achievement awards for established and new investigators to be presented at the 13th European ISSX Meeting in June 2015 in Glasgow. Visit www.issx.org/nominations for details and to submit a nomination.

For complete information about travel to Glasgow, dining, culture, sightseeing, and more, visit www.peoplemakeglasgow.com

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The International Society for the Study of Xenobiotics (ISSX) is the premier international scientific organization for researchers interested in the metabolism, disposition, and transport of xenobiotics and in other related disciplines. Our mission is to promote scientific development and to foster communication among researchers worldwide.

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June 22 – 25, 2015 | Glasgow, Scotland

Register today for the 13th European ISSX Meeting

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