ISSX President’s Message

Volume 36 Issue 1, 2016

As I begin my presidency, I would first like to thank my predecessor, John Miners, for his diligence and advice over the last two years while I served as President-Elect. John is a hard act to follow! Council has also undergone change in the new year. We say valete and many thanks to Ann Daly, Larry Marnett, and Andrew Parkinson; and salvete and congratulations on their appointment to Sonia de Morais, Uwe Fuhr, Griff Humphreys, and Mike Zientek. Jim Halpert takes over from Andrew Parkinson as Treasurer and Scott Obach takes over from Allan Rettie as the incoming chair of the Scientific Advisory Committee (SAC) and is ex officio to Council. New ISSX committee members will be announced soon. Last, but not least, I am looking forward to working with Tom Baillie, Council’s new President-Elect.

The primary event for ISSX members to look forward to in 2016 is the rapidly approaching 11th International ISSX Meeting in Busan, Korea, June 12-16. Our Korean colleagues, led

by Professor Jae-Gook Shin, have prepared an outstanding scientific and social program and, if you have not done so already, I encourage you to register to attend! This fall, ISSX will also host a workshop on Human Pharmacokinetic Predictions in Boston, Massachusetts, USA, co-chaired by Yingying Guo and Jin Zhou.. Looking further ahead to 2017, we will have the 14th European Meeting in Cologne, Germany, chaired by Uwe Fuhr; the 21st North American Meeting in Providence, Rhode Island, USA, chaired by Jash Unadkat; followed in 2018 by the 6th Asia Pacific Meeting in China and the 22nd North American Meeting in Montreal, Canada. Many thanks to everyone who has been involved on the meeting organizing committees – your time commitment and efforts are greatly appreciated.

Arising from ISSX’s strategic planning session in October 2015, Council has decided to establish special interest groups within the Society. These groups will be designed to enhance

ISSX’s scope by increasing its outreach to members and providing a mechanism for members to have more direct involvement with the Society and its activities. By focusing on specific aspects of xenobiotic research, each group will also provide a vehicle for more systematic meeting program planning in conjunction with the organizing committees and the SAC. Look for an official announcement from ISSX in the coming months! Other aspects of the strategic plan to be implemented moving forward include continued efforts to help new investigators develop their careers, the enhancement of the academia/industry interface, and the establishment of an ambassador program to promote ISSX at national and regional DMPK meetings.

I look forward to seeing you in Busan!

By Geoff Tucker, ISSX President

Book Review: New Horizons in Predictive Drug Metabolism and Pharmacokinetics

ISSX Welcomes New Members

In Memoriam: David A. Flockhart, Ph.D., M.D.

Join us in Busan, Korea

Save the Date for the ISSX Workshop

IQ Consortium DMLG Celebrates its Fifth Anniversary

ISSX Leadership Spotlight

Renew Your Membership

Stay Connected

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NEW HORIZONS IN PREDICTIVE DRUG METABOLISM AND PHARMACOKINETICSEditor: A.G.E. WilsonRoyal Society of Chemistry422 pp., ISBN-13: 978-1-78262-237-6, 2016

Are we now at a stage where we can efficiently and accurately predict the metabolites that will be formed from a drug molecule as it passes through the body? Most of the pathways of drug metabolism have been established for many years, a lot of the factors influencing absorption and distribution are known, and computer software sophistication has increased enormously. Nevertheless, a few surprises still emerge from time to time (e.g. Chem Res Toxicol 2001, 14: 611-650; J Biol Chem 2014, 288: 17065-17073; Xenobiotica 2014, 44; 666-676). How convenient it would be if computerized systems could assist and foretell these events and maybe circumvent unnecessary and costly exploration. As stated in the cover notes of the book, “Drug metabolism, pharmacokinetics and toxicokinetics as determinants of drug attrition and the safety of xenobiotics are critically important. Readers will find a thorough exploration of their predictive role in impacting drug discovery and development and in improving the success rate and safety assessment of pharmaceuticals and industrial or occupational chemicals.” This book, one in the “RSC Drug Discovery Series,” is instructive and thorough, bringing a wealth of information to the reader. It is recommended to those within the field and also those who are about to embark on such a career.

The chapter titles are as follows: “How physicochemical properties of drugs affect their metabolism and clearance;” “Role of solubility, permeability and adsorption in drug discovery and development;” “Models for nonspecific binding and partitioning;” “Cytochrome P450 mediated drug metabolism;” “Non-cytochrome P450 enzymes and glucuronidation;” “Metabolite profiling;” “Application of humanised and other transgenic models to predict human response to drugs;” “Stem cells and drug metabolism;” “Chemically reactive versus stable drug

metabolites – role in adverse drug reactions;” “Integrating metabolism and toxicity properties;” “Metabolomics-based approaches to determine drug metabolite profiles;” “Drug-drug interactions – regulatory and theoretical considerations and an industrial perspective;” “Drug-drug interactions – computational approaches;” “Induction of hepatic cytochrome P450 enzymes – importance in drug development and toxicity;” “Current status and implications of transporters – QSAR analysis method to evaluate drug-drug interactions of human bile salt export pump (ABCB11/BSEP) and prediction of intrahepatic cholestasis risk;” “Formulation of optimizing bioavailability;” “Systems pharmacology modelling;” and “Pharmacokinetic-pharmacodynamic modelling in drug development with special reference to oncology.”

Reviewed by:Steve MitchellFaculty of MedicineImperial College LondonLondon SW7 2AZ, UK

Book Ordering Information:Royal Society of ChemistryThomas Graham HouseScience Park, Milton RoadCambridge, CB4 0WF, UKTel: +44 (0)1223 420066Fax : +44 (0)1223 420247Email: books@rsc.org Website: rsc.org

USA and Canada Ingram Publisher ServicesCustomer Service, Box 63114 Ingram BlvdLa Vergne, TN 37086, USAipage.ingramcontent.comTel: +1 (866) 400 5351Fax: +1 (800) 838 1149Email: ips@ingramcontent.com

Book Review

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CHECK OUT THE ISSX CAREER CENTER

With the ISSX Career Center, over 1,000 jobs in industry and academia are at your fingertips!

Visit issx.org/career to learn more about recently-posted jobs applicable to your expertise and set-up personalized job alerts to help you manage your career!

ISSX Welcomes New 2016 MembersTakanori Akazawa, Shionogi & Co., Ltd., Japan

Laishun Chen, Allergan, Inc., United States

Chih Tung Chiu, Holy Stone Healthcare Co., Ltd., Taiwan

Paresh Chothe, Vertex Pharmaceuticals, Inc., United States

Panudda Dechwongya, Mahidol University, Thailand

Andre Luis Dias Araujo Mazzari, University College London, United Kingdom

Narayan Garimella, India

Kenta Haraya, Chugai Pharmabody Research Pte. Ltd., Singapore

Soichiro Ito, JT, Japan

Kiho Lee, Korea University, Korea

Junho Lee, Chonnam National University, Korea

Yao Lu, The Chinese University of Hong Kong, China

Toshiro Niwa, Shujitsu University, Japan

Shigeru Ohmori, Shinshu University Hospital, Japan

Robert Pelletier, University of Washington, United States

Hiromi Sato, Chiba University, Japan

Michelle Schaefer, Boehringer Ingelheim Pharma GmbH & Co. KG, Germany

Hiroshi Sugimoto, Takeda Pharmaceutical Company, Ltd., Japan

Jieun Yun, Korea Research Institute of Bioscience & Biotechnology, Korea

JOIN THE ISSX NEW INVESTIGATOR FORUM

Have you joined ISSX’s New Investigator Forum? The forum was established to encourage new investigators, those within 5–10 years of their highest-earned degree, to network

and share ideas, research, photos, and more! Please visit issx.org/group/newinvestigators

and sign in with your ISSX username and password to join the Forum and to learn more. We encourage you to leave feedback on what features you would like to see and how ISSX

can better serve graduate students and recent postdocs.

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SUBMIT YOUR

ISSX MEETING PHOTOS

ISSX invites you to submit your meeting photos for consideration in ISSX’s marketing materials, including email promotions and

social media posts. You may send your meeting photos to information@issx.org.

Please be sure to include the meeting name, year, and a brief description

of the photo with your submission.

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IN MEMORIAMDavid A. Flockhart, Ph.D., M.D. (1952–2015)ISSX has learned of the passing of David A. Flockhart, Ph.D., M.D. Dr. Flockhart came to Indiana University in the summer of 2001 as the Chief of the Division of Clinical Pharmacology. He previously worked at Georgetown University Medical Center, where he served as the Francis Cabell Brown Chair and Chief of the Division of Clinical Pharmacology and Director of the Pharmacogenetics Core Laboratory. His research was focused on clinically-relevant applications of pharmacogenetics and drug interactions.

Dr. Flockhart grew up in Edinburgh, Scotland and took Honors in Biochemistry at the University of Bristol, England. He subsequently obtained a Ph.D. from the Welsh National School of Medicine, and an M.D. from the University of Miami School of Medicine. He performed a residency in internal medicine at Georgetown University

Medical Center, and after a year as Chief Medical Resident, he completed a fellowship in Clinical Pharmacology in the Division of Clinical Pharmacology at Georgetown University Medical Center.

He published more than 250 articles, reviews, and book chapters, and was a member of many prestigious professional organizations. He received numerous awards, including the Leon I. Golberg Memorial Lecture Series Award from the University of Chicago, the Rawls-Palmer Award for Progress in Medicine from the American Society for Clinical Pharmacology and Therapeutics, and the Nathaniel T. Kwit Memorial Distinguished Service Award from the American College of Clinical Pharmacology. Over the course of his career, he became one of the foremost authorities on drug interactions and reactions.

ATTENDING PROVIDES YOU THE OPPORTUNITY TO....

• Participate in your choice of multiple short courses designed to deliver a broad-based educational experience;

• Hear outstanding lectures delivered by leading scientists who will share the latest developments in their areas of research;

• Gain recognition and feedback on your research by submitting an abstract and presenting a poster;

• Avail yourself of the many opportunities for substantive conversation and networking with scientists worldwide;

• Meet with our exhibitors who will showcase the products and services that could be helpful solutions for you in your research and development; and

• Explore Busan with its numerous tourism attractions, white, sandy beaches, excellent dining, shopping, and more!

MEETING ORGANIZING COMMITTEE

Jae-Gook Shin, Meeting Chair Inje University College of Medicine,

Korea

Hea-Young Cho

CHA University, Korea

Young-Jin Chun

Chung-Ang University, Korea

Ann Daly

Newcastle University,

United Kingdom

Zhuohan Hu

Research Institute for Liver Diseases

(Shanghai) Co. Ltd., China

Hiroyuki Kusuhara

The University of Tokyo, Japan

In-Jin Jang

Seoul National University College

of Medicine, Korea

Dong Hyun Kim

Inje University College of Medicine,

Korea

Jeong-Mi Kim

Ministry of Food and Drug Safety,

Korea

Christie Lee

Lee Convention, Korea

Hoi Young Lee

College of Medicine, Konyang

University, Korea

John O. Miners

Flinders University School

of Medicine, Australia

R. Scott Obach

Pfizer Inc., United States

Hyun-Joo Shim

Donga-ST Research Institute,

Korea

Ikumi Tamai

Kanazawa University, Japan

Geoff Tucker

University of Sheffield,

United Kingdom

Young-Ran Yoon

Kyungpook National University

School of Medicine and KNU

Hospital, Korea

INVITATION TO ATTEND

Dear Colleagues:

It is my pleasure to invite you to participate in the 11th International Society for the Study of Xenobiotics (ISSX) Meeting which will be held in Busan, Korea, June 12-16, 2016. The Meeting Organizing Committee is committed to hosting the scientific must-attend event of 2016, with a broad range of highly-relevant short courses, symposia, poster presentations, and a lively social calendar of networking events and sightseeing activities.

The 11th International ISSX Meeting will showcase important research highlighting ADME in new drug development within the theme of “The Science of Xenobiotics in the Era of Personalized Medicine.” Those involved at any level in the metabolism and disposition of drugs and other chemicals will benefit from attendance. The relaxed and friendly environment will offer both a professionally- and personally-rewarding experience, allowing for dialogue and exchange of scientific expertise among the world’s leading experts in drug/xenobiotic research.

This meeting will be held at the Busan Exhibition and Convention Center (BEXCO), a world-class convention facility located in the heart of the stunning Haeundae Beach Resort area. The five-star Paradise Hotel is the official headquarters hotel of the meeting. With a modern interior, up-to-date amenities, and oceanfront terraces embracing beautiful views of the harbor, it is the obvious choice for our meeting delegates to enjoy scenic Busan.

Busan is Korea’s second largest city. It is a port city with exquisite beaches and an abundance of fresh seafood. It is also rich in culture and history, with the UN Memorial Cemetery, various temples, many colorful markets, and sightseeing attractions including the world’s largest department store! First-time visitors to Busan are often surprised by how the locals have captured the essence of a buzzing metropolis but retain the hospitality of a country town.

I hope you will accept my invitation to participate in the 11th International ISSX Meeting and I look forward to welcoming you and your colleagues to beautiful “Dynamic Busan.”

See you in June!

Sincerely yours,

Jae-Gook Shin, M.D., Ph.D.Meeting Chair, 11th International ISSX Meeting Inje University College of Medicine, Busan, Korea

Join ISSX in Busan, Korea

PRELIMINARY PROGRAMThis program is subject to change. View the full scientific program online at issxbusan2016.org.

THURSDAY, JUNE 1611th International ISSX Meeting Awards Presentations

and Lectures

Concurrent Symposia

Symposium 13: Update on Drug Interaction Studies: From In Silico to Clinical

Symposium 14: Drug Metabolism in the Era of Precision Medicine

Symposium 15: UDP-Glucuronosyltransferase and Drug Glucuronidation

Special Lecture: The Move of PBPK from Academic Nicety to Industrial Necessity– Amin Rostami, Certara and University of Manchester, United Kingdom

WEDNESDAY, JUNE 15Plenary Lecture 3: The Role of Toxic Lipids in Metabolic Disease– Frank Gonzalez, National Institutes of Health, United States

Concurrent Symposia

Symposium 9: Proteomic Analysis of Phase 1 and Phase 2 Drug Biotransformation Pathways and Transporters

Symposium 10: Pharmaco-metabolomics as Biomarkers for Personalized Medicine

Symposium 11: Analysis and Mechanisms of Disease-related Transporters

Symposium 12: Pharmacogenomics for Personalized Pharmacotherapy: Update on Clinical Implementation

Asia Pacific Regional Session: Xenobiotic Study: Significant Contributions from Asia-Pacific Scientists

Poster Award Finalist Oral Presentations

SUNDAY, JUNE 12Concurrent Morning Short Courses*

Short Course 1: ADME Characterization of Biologics and Antibody Drug Conjugates (ADC)

Short Course 2: Principles of In Vitro – In Vivo Extrapolation in the Application of PBPK Modelling

Concurrent Afternoon Short Courses*

Short Course 3: Drug Induced Liver Injury – How Mechanistic Insights Aid Preclinical Detection and Prediction

Short Course 4: Modeling Approaches to the Prediction of Drug-drug Interactions

Keynote Lecture: Drug Transporters: Starring Roles in New Drug Discovery and Development – Yuichi Sugiyama, RIKEN, Japan

MONDAY, JUNE 13Plenary Lecture 1: Drug Discovery and Development: Looking for Needles in a Hay Stack – Marcel Hop, Genentech, United States

Concurrent Symposia

Symposium 1: Disposition of Antibody Drug Conjugates (ADCs): Current Understanding and Challenges

Symposium 2: Redox Modulation of Xenobiotic Metabolism and Toxicity

Symposium 3: Humanized or Transgenic Animal Models in Drug Metabolism and Toxicology Studies

Symposium 4: Oncology-focused Modelling and Simulation in Drug R&D

Symposium 5: Emerging Roles of CYP4 Family Enzymes in Endogenous Metabolism and Disease

Symposium 6: ITC Symposium on Drug Transporters: Best Practice in Drug Development

TUESDAY, JUNE 14Plenary Lecture 2: Pharmacogenomics: Relevance to Personalized Medicine – Munir Pirmohamed, University of Liverpool, United Kingdom

Concurrent Symposia

Symposium 7: The Regulation of Pharmacogenomics in Clinical Drug Development

Symposium 8: Non-HLA Genetic Risk Factors in Idiosyncratic Adverse Drug Reactions

Free Afternoon for Social Events and Activities

* Short course registration is available for an additional fee. All short course attendees receive short course materials and a complimentary course lunch.

Register today at: issx.org/busan/registerMeeting website: issxbusan2016.org

ATTENDEE INFORMATION View complete attendee information online at issxbusan2016.org.

Abstract SubmissionsPoster presentations are an integral component of ISSX meetings. We encourage all those involved in the fields of metabolism, pharmacology, toxicology, molecular biology, and other related disciplines to submit an abstract for a poster presentation at the 11th International ISSX Meeting. General abstract poster sessions will be held Monday, June 13 - Wednesday, June 15 in the exhibit hall.

Exhibits and SponsorshipsThis meeting will feature an exhibition showcasing the products and services that researchers need to advance their work. The exhibition begins with the welcome reception on Sunday evening and continues throughout the meeting. Meet with representatives from top suppliers and maximize the value of your attendance! Companies interested in exhibiting, sponsoring, or advertising are invited to review the exhibitor prospectus and application online at issxbusan2016.org.

ISSX Awards ProgramThe ISSX awards program was established to recognize excellent scientific and service achievements in the scientific fields covered by the Society. The call for nominations is now open through March 31 for the following awards to be presented at the 11th International ISSX Meeting:

The R.T. Williams Distinguished Scientific Achievement Award Sponsored by Charles Crespi and FamilyPresented to an ISSX member or non-member from any region who has made substantial and seminal scientific contributions to the field over a sustained period. The focus of this award is the individual’s scientific accomplishments and it is intended to recognize the best in the field internationally.

The Frederick J. Di Carlo Distinguished

Service Award

Presented to an ISSX member from any region who has a record of important service to the Society and its goals.

Hotels, Travel, and Visa

Hotels and Travel

Lee Convention is our official partner in Busan, offering ISSX meeting attendees a variety of lodging options to fit any budget. There are several options available to travel to and from Busan, Korea, including flights, trains, or ferry.

Visa Information

All visitors to Korea must have a valid passport and visa. For details about obtaining a visa, please be sure to visit the meeting website.

Social ProgramISSX leadership and the Meeting Organizing Committee invite attendees of the 11th International ISSX Meeting to participate in the social program of the meeting.

Opening Ceremony and Welcome Reception

Attendees are cordially invited to join us at the Opening Ceremony on June 12. After the ceremony and presentation, meet with old friends and make new acquaintances at the welcome reception while you enjoy hors d’oeuvres and beverages and meet with the exhibiting companies. This event is complimentary for full meeting registrants and their registered guests.

New Investigators Session and Reception

Calling all new investigators! This special session and reception for new investigators, those within ten years of having earned their highest degree, provides a wonderful opportunity to learn from each other while you build new friendships in a socially-inviting environment. This event, held June 13, is complimentary for full meeting registrants.

Banquet

The banquet dinner will be held at The Bay 101 Yacht Club—a 15,000 square food marine complex located at Haeundae Beach. The Haeundae area is a cosmopolitan region in Busan surrounded by the sea, mountians, and contemporary buildings and the views from our private event space will be spectacular as the night comes and the city's lights illumiate our banquet dinner. A separate registration fee applies.

The deadline for final abstract submissions is Monday, March 14 at 11:59 p.m. Eastern Time (US).

The nomination submission deadline for these awards is Thursday, March 31.

MEETING REGISTRATION FEES

SHORT COURSE REGISTRATION FEES

Register today at: issx.org/busan/register

Meeting website: issxbusan2016.org

Abstract submissions: issx.org/busan/abstract

Award nominations: issx.org/award

* Any registrants from countries listed by the World Bank as lower-income and lower-middle-income economies may register for this category (issx.org/designated).

REGISTRATION TYPEREGULAR

By June 1ONSITE

June 2–June 16

ISSX Member $735 $815

Non-Member $895 $965

Registrant from China $450 $500

Registrant from a Designated Country* $350 $380

Student/Postdoc* $275 $300

Student/Postdoc from a Designated Country* $75 $100

REGISTRATION TYPEREGULAR

By June 1ONSITE

June 2–June 16

ISSX Member $235 $260

Non-Member $285 $335

Registrant from China $150 $175

Registrant from a Designated Country* $125 $150

Student/Postdoc* $125 $150

Student/Postdoc from a Designated Country* $75 $100

Save the Date for the ISSX WorkshopTranslating Preclinical Data to Human Clearance and Pharmacokinetics

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The ISSX Workshop on Human Pharmacokinetic Predictions on October 27–28, 2016 will deliver state-of-the-art science in a focused meeting. Key sessions will include:

• Gap analyses in human PK/clearance prediction at drug discovery and development stages;

• Methodological aspects of clearance prediction for low clearance and highly-bound compounds;

• Predicting clearance mediated by non-CYP metabolizing enzymes;

• Quantitative assessment of hepatobiliary transporter-mediated clearance; and

• Human PK/clearance prediction in special populations.

Workshop Description

Our ability to accurately predict human clearance and pharmacokinetics (PK) is a critical component of drug discovery and development. These predictions impact projection of first human dose and potential for drug-drug interactions, which are important attributes of the risk-benefit assessment framework for candidate selection and the planning of early clinical studies. Furthermore, consideration can be given to the need for dose adjustment in patients versus healthy volunteers and for special populations such as pediatric, hepatic or renally-impaired, and genetic subpopulations. Predictions can be challenging as a result of potential in vitro-in vivo discrepancies and inter-species differences in the specificities and abundance of enzymes and transporters. Moreover, new challenges for human PK/clearance prediction continue to arise. For example, CYP-mediated clearance is being reduced by chemical manipulation in drug discovery only to be replaced by clearance by drug metabolizing enzymes with which we have less scaling experience. This workshop aims to provide fundamental knowledge on current approaches, examine the utility of in vitro and in vivo experimental systems, discuss modeling

approaches in human PK/clearance prediction, focus on the current challenges, and offer next steps. The ultimate goal is to facilitate formulation of practical strategies utilized in the pharmaceutical industry for human PK/clearance prediction based on in vitro and animal data, in combination with modeling methods.

The aim of this workshop is to:

• Update the current status and challenges in prediction of human PK;

• Assess the application and regulatory perspectives of PBPK modeling;

• Examine state-of-the-art in vitro technologies, combined with physiologically-based models, to address clearance prediction for low clearance and highly bound compounds;

• Address challenging issues and next steps in PK/clearance prediction for non-CYP enzymes, including UGTs, aldehyde oxidase, and carboxylesterases;

• Discuss approaches to predict human hepatobiliary transporter-mediated clearance; and

• Examine experimental and modeling/simulation approaches in predicting PK/clearance in special populations for compounds of different BDDCS categories.

All pharmaceutical scientists, academicians, and regulatory professionals interested in learning about prediction approaches, developing their expertise, and gaining a more complete appreciation of using a model-based approach to better understand predicting PK/clearance are encouraged to attend. A poster session will highlight cutting-edge methodologies in human PK/clearance prediction.

Workshop registration is now open! Additional details will be posted on ISSX’s website at issx.org/workshop as they become available.

WORKSHOP ORGANIZING COMMITTEE

Aleksandra Galetin

University of ManchesterStephen D. Hall

Eli Lilly and CompanyDonald Tweedie

Boehringer Ingelheim

Yingying Guo, Co-ChairEli Lilly and Company

Jin Zhou, Co-ChairBoehringer Ingelheim

The International Consortium for Innovation & Quality in Pharmaceutical Development (IQ Consortium, iqconsortium.org) is a technically-focused organization of pharmaceutical and biotechnology companies whose mission is to advance science and technology to augment the capability of member companies to develop transformational solutions that benefit patients, regulators, and the broader R&D community. The IQ Consortium is comprised of eleven Leadership Groups focused on diverse components of drug discovery and development such as drug metabolism, clinical pharmacology, preclinical safety, 3Rs, active pharmaceutical ingredients, drug products, etc. The Drug Metabolism Leadership Group (DMLG) has been particularly active and has created many working groups and discussion groups to tackle specific scientific and regulatory issues. The mission of the DMLG is to advance ADME sciences through participants’ collective experience and resources in order to accelerate the delivery of safe and efficacious medicines to patients.

Over the past five years, the DMLG has collaborated cross-functionally within IQ and with external groups and regulators in identifying topics of critical and broad interest. Completed and ongoing initiatives include: drug-drug interactions due to metabolites (Contribution of Metabolites to P450 Inhibition–Based Drug–Drug Interactions: Scholarship from the Drug Metabolism Leadership Group of the Innovation and Quality Consortium Metabolite Group. Drug Metab. Dispos. 2015, 43:620-630), physiologically-based pharmacokinetic modeling (Physiologically based pharmacokinetic modeling in drug discovery and development: a pharmaceutical industry perspective. Clin. Pharmacol. Ther. 2015, 97:246-262) and joint workshop with the FDA), pharmacokinetic/pharmacodynamic modeling and simulation, therapeutic protein drug-drug interactions (joint workshop with the FDA: “Workshop on Recent Advances in the Investigation of Therapeutic Protein Drug-Drug Interactions: Preclinical and Clinical Approaches”), 4 -hydroxycholesterol as an endogenous probe for clinical CYP3A induction, new chemical entities as the victim of drug-drug interactions, transporter interactions profiling of antibody-drug conjugates, in silico ADME modeling, microsampling, and microphysiological platforms. Details of these initiatives, as well as other IQ Consortium activities, events, and publications, can be found at iqconsortium.org.

IQ Consortium DMLG Celebrates its Fifth Anniversary

IQDMLG PUBLICATIONS

Critical review of preclinical approaches to investigate cytochrome p450-mediated therapeutic protein drug-drug interactions and recommendations for best practices: a white paper. Evers R1, Dallas S, Dickmann LJ, Fahmi OA, Kenny JR, Kraynov E, Nguyen T, Patel AH, Slatter JG, Zhang L. Drug Metab Dispos. 2013 Sep; 41(9):1598-609. doi: 10.1124/dmd.113.052225. Epub 2013 Jun 21.

Therapeutic protein drug-drug interactions: navigating the knowledge gaps-highlights from the 2012 AAPS NBC Roundtable and IQ Consortium/FDA workshop. Kenny JR1, Liu MM, Chow AT, Earp JC, Evers R, Slatter JG, Wang DD, Zhang L, Zhou H. AAPS J. 2013 Oct; 15(4):933-40. doi: 10.1208/s12248-013-9495-1. Epub 2013 Jun 21.

Evaluation of various static and dynamic modeling methods to predict clinical CYP3A induction using in vitro CYP3A4 mRNA induction data. Einolf HJ1, Chen L2, Fahmi OA3, Gibson CR4, Obach RS3, Shebley M5, Silva J6, Sinz MW7, Unadkat JD8, Zhang L9, Zhao P9. Clin Pharmacol Ther. 2014 Feb; 95(2):179-88. doi: 10.1038/clpt.2013.170. Epub 2013 Aug 29.

Evaluation of various static in vitro-in vivo extrapolation models for risk assessment of the CYP3A inhibition potential of an investigational drug. Vieira ML1, Kirby B2, Ragueneau-Majlessi I2, Galetin A3, Chien JY4, Einolf HJ5, Fahmi OA6, Fischer V7, Fretland A4, Grime K8, Hall SD4, Higgs R4, Plowchalk D6, Riley R9, Seibert E10, Skordos K11, Snoeys J12, Venkatakrishnan K13, Waterhouse T4, Obach RS6, Berglund EG14, Zhang L1, Zhao P1, Reynolds KS1,Huang SM1. Clin

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Pharmacol Ther. 2014 Feb; 95(2):189-98. doi: 10.1038/clpt.2013.187. Epub 2013 Sep 18.

Contribution of metabolites to p450 inhibition-based drug-drug interactions: scholarship from the drug metabolism leadership group of the innovation and quality consortium metabolite group. Yu H1, Balani SK2, Chen W2, Cui D2, He L2, Humphreys WG2, Mao J2, Lai WG2, Lee AJ2, Lim HK2, MacLauchlin C2, Prakash C2, Surapaneni S2, Tse S2,Upthagrove A2, Walsky RL2, Wen B2, Zeng Z2. Drug Metab Dispos. 2015 Apr; 43(4):620-30. doi: 10.1124/dmd.114.059345. Epub 2015 Feb 5.

Physiologically based pharmacokinetic modeling in drug discovery and development: a pharmaceutical industry perspective. Jones HM1, Chen Y, Gibson C, Heimbach T, Parrott N, Peters SA, Snoeys J, Upreti VV, Zheng M, Hall SD. Clin Pharmacol Ther. 2015 Mar; 97(3):247-62. doi: 10.1002/cpt.37. Epub 2015 Jan 9.

Preclinical Pharmacokinetic/Pharmacodynamic Modeling and Simulation in the Pharmaceutical Industry: An IQ Consortium Survey Examining the Current Landscape. Schuck E1, Bohnert T, Chakravarty A, Damian-Iordache V, Gibson C, Hsu CP, Heimbach T, Krishnatry AS, Liederer BM, Lin J, Maurer T, Mettetal JT, Mudra DR,Nijsen MJ, Raybon J, Schroeder P, Schuck V, Suryawanshi S, Su Y, Trapa P, Tsai A, Vakilynejad M, Wang S, Wong H. AAPS J. 2015 Mar; 17(2):462-73. doi: 10.1208/s12248-014-9716-2. Epub 2015 Jan 29.

Implementing Dried Blood Spot Sampling for Clinical Pharmacokinetic Determinations: Considerations from the IQ Consortium Microsampling Working Group. Evans C1, Arnold M, Bryan P, Duggan J, James CA, Li W, Lowes S, Matassa L, Olah T, Timmerman P, Wang X, Wickremsinhe E, Williams J, Woolf E, Zane P. AAPS J. 2015 Mar; 17(2):292-300. doi: 10.1208/s12248-014-9695-3. Epub 2014 Dec 9.

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For more than 150 years, a very special passion has driven the people of Merck. Our goal is to develop medicines, vaccines, and animal health innovations that will improve the lives of millions. Still, we know there is much more to be done. And we’re doing it, with a long-standing commitment to research and development. We’re just as committed to expanding access to healthcare and working with others who share our passion to create a healthier world. Together, we’ll meet that challenge. With all our heart.

MEDICAL BREAKTHROUGHS MAY COME OUT OF THE LAB.BUT THEY BEGIN IN THE HEART.

For more information about getting Merck medicines and vaccines for free, visit merckhelps.com or call 800-727-5400. Copyright © 2014 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. All Rights Reserved. CORP-1060080-0090 12/14

IQDMLG PUBLICATIONS (continued)

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The Council serves as the Society’s governing leadership body and works to further ISSX’s mission to advance research and education on the interplay of living systems with medicines and chemicals for the benefit of society worldwide. At the end of 2015, the following members of Council completed their terms. The Society wishes to recognize them for their service over the years:

John Miners, Flinders University School of Medicine, Adelaide, AustraliaPresident, 2014–2015President-Elect, 2012–2013Councilor, 2009–2011; 2004–2005; 1988–1991

Andrew Parkinson, XPD Consulting, Shawnee, Kansas, USATreasurer, 2014–2015Treasurer-Elect, 2012–2013Councilor, 1994–1997

Ann Daly, Newcastle University, Newcastle Upon Tyne, UKCouncilor, 2012–2015

Lawrence Marnett, Vanderbilt University School of Medicine, Nashville, Tennessee, USACouncilor, 2014–2015

Allan Rettie, University of Washington, Seattle, Washington, USAScientific Affairs Committee Chair, Ex Officio to Council, 2012–2015, Councilor, 2004–2005

ISSX Welcomes New Council Members

Voting in an ISSX election is an important membership right and determines the future leadership of the Society. ISSX held an election in 2015 for members to select the President-Elect, Treasurer-Elect, and four members of Council. Tom Baillie of the University of Washington, Seattle, Washington, USA was elected to serve a two year term as the President-Elect. He will assume the presidency in 2017. Maria Almira Correia of the University of San Francisco in San Francisco, California, USA was elected to serve a second term. R. Scott Obach of Pfizer, Inc., Groton, Connecticut, USA succeeded Allan Rettie as the chair of the Scientific Affairs Committee and ex officio to Council.

The following individuals were elected for the remaining positions and are new to ISSX Council:

Sonia de Morais, AbbVie, Inc., Chicago, Illinois, USATreasurer-Elect

Sonia de Morais holds B.S. and M.S. degrees in Pharmacy from the University of Sao Paulo, Brazil, and a Ph.D. in Pharmacy from the University of Toronto, Canada. Her postdoctoral research focused on the Ah receptor while at the

Department of Pharmacology, University of Toronto; followed by research on the identification of genetic polymorphisms in the CYP2C19 gene at the NIEHS, in Research Triangle Park, North Carolina, USA. This discovery was patented by the NIH in 1994.

Sonia joined the pharmaceutical industry in 1995, initially at Boehringer Ingelheim in Ridgefield, Connecticut where she was a Group Leader of Drug Metabolism. She joined Pfizer, Inc. in 1999 and led the development of in vitro technologies to understand drug transporters and other ADMET processes, as well as being responsible for the support of Hit-to-Lead Discovery project teams. She received the National Hispanic Corporate Achievers award from Pfizer in 2007.

Sonia has an extensive scientific publication record and has been invited to present and chair sessions at multiple international conferences in the areas of drug transporters, enzyme induction, ADMET screening, Hit-to-Lead and discovery support.

Sonia obtained an Executive M.B.A. from Rensselaer Polytechnic Institute in 2003. The concepts of finance, organizational behavior, and other business-relevant topics were instrumental to Sonia’s management career progression in the pharmaceutical industry.

Sonia joined Abbott Laboratories in Chicago in December 2008. The Pharmaceutical Division of Abbott separated from the company and became AbbVie, Inc. in 2013. Sonia is currently the Director of Drug Metabolism and Pharmacokinetics at AbbVie, Inc. Her department employs about 55 scientists responsible for scientific studies from early discovery to NDA, for both small molecules and antibody-drug-conjugates.

ISSX Leadership Spotlight

11th International

ISSX Meeting

Busan Exhibition and Convention Center

Busan, KoreaJune 12–16, 2016

Meeting Chair: Jae-Gook Shin, M.D., Ph.D.

ISSX Workshop on

Human Pharmacokinetic

Predictions

Sheraton Boston HotelBoston, Massachusetts, USA

October 27–28, 2016

Workshop Co-Chairs: Yingying Guo, Ph.D. and

Jin Zhou, Ph.D.

14th European

ISSX Meeting

Gürzenich KölnKöln, Germany

June 26–29, 2017

Meeting Chair: Uwe Fuhr, Ph.D.

21st North American

ISSX Meeting

Rhode Island Convention Center

Providence, Rhode IslandSeptember 24–28, 2017

Meeting Chair: Jashvant Unadkat, Ph.D.

PLEASE JOIN ISSX AT THE

FOLLOWING UPCOMING MEETINGS

Sonia has served on ISSX’s Scientific Advisory Committee for the last four years and was a member of the meeting organizing committee for the 18th North American ISSX meeting in Dallas, Texas, USA in 2012.

Sonia’s vision is to further strengthen ISSX’s impact on the field of xenobiotic research in academia and industry. In recent years, the Society has developed to being truly international and has provided venues for scientific exchange, collaborations, and career enrichment for many scientists, from academia, regulatory agencies, and industry. She believes that ISSX has the potential to become the global organization of choice in xenobiotic research.

Uwe Fuhr, University Hospital of Cologne, Cologne, GermanyCouncilor

Uwe Fuhr is a citizen of Germany and attended Johann Wolfgang Goethe University in Frankfurt am Main, Germany, as an undergraduate in Medicine to obtain state registration as a physician and the degree of

“Dr. med.” After residency training in Clinical Pharmacology at the Johann Wolfgang Goethe University, he was a Postdoctoral Fellow at the Institute of Biomedical and Pharmaceutical Research in Nürnberg, Germany. In 1996, Uwe was appointed as Associate Professor and head of the Clinical Pharmacology group in the Department of Pharmacology at Medical Faculty, University of Cologne, where he is also Acting Chairman of the Department of Pharmacology since 2015. In parallel, in 2006 he co-founded the full service contract research organization

“ITECRA” (Institute for Tailored Early Clinical Research and Advice GmbH & Co. KG), where he acted as the scientific advisor until 2012.

Uwe Fuhr's research aims at the individualization of drug therapy and on developing the tools needed to this end. His lab focuses on drug metabolism using techniques spanning from electrochemistry over in vitro research to clinical studies in healthy volunteers and in patients, on drug interactions including phenotyping cocktail interaction studies, and on population pharmacokinetic/pharmacodynamic modelling. He has authored more than 150 publications.

Uwe served on the Finance Committee from 2006 to 2007 and is the Chair of the Meeting Organizing Committee for the 14th European ISSX meeting in Cologne, Germany, 2017.

Uwe is a Managing Editor and Reviews Editor of the European Journal of Clinical Pharmacology. He is a member of several learned societies and served in various functions on German clinical pharmacology organizations.

Uwe’s work has been recognized with several awards, including the "Friedrich Hartmut Dost Memorial Award 1994 of the German Society for Clinical Pharmacology and Therapy."

Uwe’s vision is to support ISSX to be the leading international, learned Society that provides communication and education in the field of understanding and predicting the actions of xenobiotics. He places great importance on the need for ISSX to support young scientists.

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William “Griff” Humphreys, Bristol-Myers Squibb, Princeton, New Jersey, USACouncilor

Griff Humphreys is currently the Executive Director of the Biotransformation Department at Bristol-Myers Squibb. He received his graduate training at the

University of Virginia in chemistry and completed a postdoctoral fellowship at Vanderbilt University at The Center in Molecular Toxicology. He then joined Bristol-Myers Squibb and has been with the company ever since. He oversees a group responsible for drug metabolism, disposition, and metabolite identification studies during the candidate optimization and drug development phases.

His interests include the consequences of reactive metabolite formation, development of new analytical methodologies for metabolite detection, reaction phenotyping of CYP and UGT catalyzed biotransformations, predictive metabolism and toxicology models, in vitro-in vivo correlations, and strategies for candidate optimization. He has co-authored over 100 refereed manuscripts and numerous reviews and book chapters.

Griff is a member of ISSX and the ACS Chemical Toxicology Division (TOXI). He is on the Editorial Advisory Boards of Drug Metabolism and Disposition and Chemical Research in Toxicology and serves as a reviewer for multiple other journals. He has served on the Executive Committee of TOXI since 2008 and most recently was the Program Chair for their 2013-2014 national meetings.

Michael Zientek, Pfizer, Inc., San Diego, California, USACouncilor

Michael A. Zientek received his B.S. from Purdue University and MPH from the University of Michigan. Michael joined Pfizer Worldwide Research and Development as a research

scientist in 1994 in a discovery enzymology role, working in the areas of cardiovascular disease and oncology where he assumed responsibilities of developing target-related kinetic assays for drug discovery. In 2001, he moved from discovery biology to Pharmacokinetics, Dynamics, and Metabolism (PDM), applying his knowledge of human physiology, enzymology, enzyme kinetics, and automation to the drug metabolism and pharmacokinetic disciplines Michael now provides PDM guidance to advance molecules through design efforts in discovery, optimizing and predicting human pharmacokinetic properties, preparing molecules for regulatory submission, and also progressing compounds through clinical proof of concept at the Pfizer R&D site in San Diego, California, USA.

Michael’s research activities have been and continue to be devoted to investigation of drug metabolizing enzymes, polymorphisms, drug-drug interactions, and human ADME of new and established xenobiotics. He has authored more than 30 publications in this area, ranging from new tools for ADME investigations to characterization of targeted therapies.

Michael has been active with a number of nonprofit scientific organizations that promote the exchange of new research findings and he brings this experience to ISSX. He has served on the steering committee of the Southern California Drug Discussion Group for the past five years and has been both Chair and Vice-Chair of the Gordon Research Conference (GRC) on Drug Metabolism. He has been an invited speaker or discussion leader at the GRC, American Association of Pharmaceutical Sciences (AAPS), ISSX, and he is a member of several professional societies. Michael has also been a peer reviewer for several journals including Drug Metabolism and Disposition, Clinical Pharmacokinetics, and Expert Opinion in Drug Metabolism and Toxicology.

Michael’s goal as an ISSX Council Member is to increase the impact and value of ISSX scientific meetings and workshops for its members, while ever-increasing the international diversity of its membership which will promote collaboration among academic, industry, and regulatory agencies to speed advancements in our sciences and xenobiotic discovery.

GET INVOLVED

Looking for more ways to be involved?

Volunteer with ISSX! If you are interested in serving the Society as part of a task

force or as a committee or Council member, ISSX wants to hear from you. Express your

interest by visiting issx.org/volunteer.

ISSX membership dues for the 2016 membership year were due on December 31, 2015. You can still renew your membership online by following these easy steps:

1. Visit issx.org/renew.

2. On the right-hand side of the page, log in with your ISSX username and password. If you do not know your username or password, you may re-set it by visiting issx.org/password.

3. Click on ***Renew Your Membership Now*** in the blue box at the top of your profile page.

4. On the next screen, you will be prompted to review and update your contact information to ensure uninterrupted communications from ISSX.

5. Upon verifying your contact information, you will be directed to the payment screen, where you may view your renewal options, including instant payment online via credit card.

If you would like to pay by check, please select the "Bill Me" option under Payment. You can access your invoice on the subsequent page, and one will be automatically emailed to you. Please print the invoice and submit it with your check payment to:

ISSX8652 Solution Center

Chicago, IL 60677-8006

If you wish to remit payment by ACH or wire transfer, please contact ISSX at information@issx.org for more details.

It’s Not Too Late to Renew Your Membership for 2016

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ISSX MEMBERS HAVE ACCESS TO A VARIETY OF

EXCLUSIVE BENEFITS INCLUDING:

• Reduced registration fees for all ISSX meetings and workshops;

• A subscription to the ISSX Newsletter that highlights Society news, member spotlights, late-breaking scientific news, and much more;

• Special journal subscription discounts to multiple scientific journals;

• The opportunity to submit and present scientific abstracts at ISSX meetings;

• Eligibility to apply for and receive travel grants to attend ISSX meetings;

• The chance to hold office, serve on a committee, and vote in ISSX elections;

• Access to online learning opportunities (coming soon!);

• And more!

Visit issx.org/renew today!

If you have any questions about renewing your membership or your membership

benefits, please contact ISSX by phone at +1-202-367-1160 or by email

at information@issx.org.

The new ISSX Marketplace (www.ISSXMarketplace.com) provides you with a quick and easy research solution when you are seeking new products and services.

Utilize the Marketplace to locate multiple vendors and let them compete for your business. Send requests for proposal directly through the site to select vendors, view their website, or contact them directly via phone or email.

Find new companies, learn about products you may not have been aware of, and simplify your purchasing process. Visit the ISSX Marketplace today and bookmark it for the next time you need to locate new vendors, products, or services.

Make sure to visitwww.ISSXMarketplace.com

and bookmark it today!

Announcing the new ISSX Marketplace

PHARMACOKINETIC OPPORTUNITIESYou know a single molecule could change the lives of millions. So you need a place that supports your

search for that molecule, without compromise. A place that doesn’t just encourage big thinking, but

demands it. A place that breaks new ground by breaking with convention. A place like Genentech’s Early

Research & Development Group. Visit careers.gene.com and search for the Job ID numbers below to

learn more and apply to these exciting opportunities in Pharmacokinetics.

Scientist/Sr. Scientist, Drug Metabolism and Pharmacokinetics – (Job ID #00442120)

You will be who will be involved in the design, execution, supervision, and interpretation of non-clinical

pharmacokinetic studies in support of discovery and development programs. These studies will enable

the selection of small molecule drug development candidates and provide detailed assessment of their

pharmacokinetic characteristics.

Scientist – Preclinical and Translational Pharmacokinetics/Pharmacodynamics (PTPK) –

(Job ID #00434278)

You will be responsible for investigating the pharmacokinetics, biodistribution, and PKPD relationships

of noveltherapeutics in preclinical models to identify lead candidates for further development, and for

bridging preclinical PKPD information to patients.

Genentech is an Equal Opportunity Employer: Minorities / Women / Disability / Veteran

Stay Connected with ISSXISSX is active on Facebook, Twitter, and LinkedIn. If you are not yet following our pages, please do so today!

Like us on Facebook!

Visit facebook.com/ISSXNews and click “Like” on the cover page.

Follow us on Twitter!

Visit twitter.com/ISSX and click “Follow.”

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Visit linkedin.com/in/ISSXNews and click “Connect.”

Want to have ISSX highlight your news? Submit your career updates, publications, and photos to information@issx.org for an opportunity to be featured on ISSX’s social media accounts.

Deadline for the submission of material to the ISSX Office:

ISSUE MATERIALS DEADLINE* RELEASE DATE

Issue 2, 2016 April 15, 2016 May 2016

Issue 3, 2016 July 15, 2016 August 2016

Issue 4, 2016 October 14, 2016 November 2016

*Subject to change

Editor Dr. Allen Cato, IIICato Research, LTD6480 Weathers Place, Suite 104San Diego, California 92121USATelephone: +1-858-452-7271Fax: +1-858-452-7784E-mail: jcato@cato.com

ISSX Newsletter is published quarterly in the spring, summer, autumn, and winter. For information concerning advertising in this publication, including rates and specifications, please visit issx.orgor contact Steve Rabeor at srabeor@issx.org.

Advertise with ISSX in the quarterly ISSX Newsletter. Rates and additional advertising opportunities are available at issx.org/advertising.

Change of AddressIf your mailing address, telephone, fax number, or e-mail has changed or will change, please let us know as soon as possible. You may update your contact information at any time using the online membership directory, which you can access in the Member Only section of the Web site. If you have forgotten your username and/or password, please contact information@issx.org.

ADVERTISE WITH ISSX

The quarterly ISSX Newsletter is an online publication featuring Society updates, scientific articles of interest, book reviews, summaries of ISSX meeting proceedings, and more. This publication is designed to update the ISSX membership on the activities and events of the

organization and to provide an information forum.

Not only is the ISSX Newsletter promoted directly to all ISSX Members, it is also available to anyone who visits the ISSX website.

Visit issx.org/advertising or contact Steve Rabeor at srabeor@issx.org.