ISSX Newsletter | Issue 1, 2019

Volume 42

Issue 1, 2019

ISSX President’s Message

By Thomas Baillie, ISSX President With the advent of the New Year, I would like to welcome to ISSX all the new members who have joined the Society for the first time, in addition to those returning members who have renewed their annual dues. At year-end 2018, ISSX membership stood at 1,014, and we hope to exceed that total this year following a membership drive that currently is in progress. We are especially interested in recruiting graduate students and postdoctoral researchers to our ranks and, as you will have read in previous editions of this Newsletter, we have implemented several initiatives intended specifically to benefit this group, e.g. the ISSX Mentorship Program and the New Investigators sessions at our conferences. I would ask you to bring these free benefits of Society membership to the attention of promising young investigators as they plan for careers in fields that involve the

study of foreign compounds in animals and humans. I would also encourage all members to consider joining one or more of the three Focus Groups (Biotransformation Mechanisms & Pathways, Bioanalysis in ADME Science, and Modeling & Simulation) that have been established to provide a forum for online discussions on relevant topics and in-person networking at our annual meetings. See the ISSX web site for information on these Focus Groups and to sign up.

Along with those of you who are new to the general membership of ISSX, I would also like to add a warm welcome to two new members of ISSX Council, namely Jash Unadkat (University of Washington) and Eric Chan (National University of Singapore), who were elected to positions vacated by Jas Sahi and Natalie Hosea who had completed their two-year terms of office at the

end of 2018.

My sincere thanks to Jas and Natalie for all of their many contributions to the Society during this period!

Thomas Baillie, Ph.D. ISSX President.

As you will have seen in the previous issue of this Newsletter, only one ISSX meeting will be held in 2019 since this year’s event is designated as an International Meeting.

Specifically, this meeting will be the 12th International ISSX Meeting, scheduled to take place in Portland, OR, from July 29-31. The meeting co-chairs, Aleksandra Galetin, Deepak Dalvie, and Hiroyuki Kusuhara, together with their Meeting Organizing Committee, have Continued on page 12

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Changes on the ISSX Council Book Reviews ISSX2019: The 12th International ISSX Meeting

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ISSX Membership Ambassador Program

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Save the Date for the December ISSX Workshop

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ISSX Mentorship Program

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21st International Conference on Cytochrome P450 (ICCP450)

New Members

Changes on the ISSX Council As the New Year begins we welcome the newest Council members Eric Chan and Jashvant (Jash) Unadkat to the ISSX Council.

Eric and Jash began their two-year terms of service on Council January 1, 2019. Eric and Jash are the first members of Council elected under the new system of region-based voting which was approved by the ISSX membership to ensure equitable geographic representation among the leadership.

Eric Chan is a pharmaceutical scientist and an associate professor in the Department of Pharmacy, National University of Singapore (2011–present). His research interests are (1) metabolism-driven systems biology modeling of diseases, pharmacology, toxicology, and mammalian host-bacteria interactions and (2) xenobiotic-derived reactive metabolite research with specific focus on interaction with biological proteins and physiological-based pharmacokinetics-pharmacodynamics (PBPK-PD) modeling of pharmacology and toxicology.

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Eric’s academic career has been developed successfully based on his active participation in meetings and workshops organized by ISSX over the years. As a Scientific Affairs Committee member of ISSX, Eric further gains experience in evaluating proposals to ensure high-quality scientific meetings and workshops via the collaborations between academia, industry, and regulatory agencies.

Jashvant (Jash) Unadkat, Ph.D. is the Milo Gibaldi Endowed Professor in the Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle. Jash is a dual US and British citizen. He received his Bachelor degree in Pharmacy (B. Pharm.) from the University of London (1977), his Ph.D. from the University of Manchester (1982; advisor Prof. Malcolm Rowland) and his postdoctoral training in Clinical Pharmacology at the University of California at San Francisco (1982–85; advisor the late Dr. Lewis B. Sheiner).

Jash has served on numerous committees within scientific organizations (e.g. AAPS) including NIH review panels and as an Associate Editor for the Journal of Pharmaceutical Sciences. He has organized or co-organized numerous national and international conferences, the most recent being the 21st North American ISSX Meeting in Rhode Island. He was also the co-organizer of the ISSX-sponsored workshop on “Towards Reaching a Consensus on Using Quantitative LC-MS/MS Proteomics in Translational DMPK/PD Research,” held September 27–28, 2018 in Cambridge, Mass.

ISSX also wishes to extend our thanks and appreciation for the work of our outgoing Council members, Natalie Hosea and Jasminder (Jas) Sahi.

Natalie Hosea completed her second term of service on the ISSX Council at the end of 2019. Natalie concurrently served as Chair of the ISSX Membership Affairs Committee and was therefore crucial in providing timely membership related matters directly to Council.

She served as a member of the Meeting Organizing Committee for the joint ISSX/JSSX meeting in 2014, was an inaugural member of the Continuing Education Committee, and has served as a moderator for ISSX webinars.

Jasminder (Jas) Sahi served four years as a member of Council. Jas has been instrumental to the governance of the Society in many ways and recently served as one of the chairpersons of the 6th Asia Pacific ISSX Meeting held in Hangzhou, China. Jas will remain active with ISSX in her role as Chair of the still new ISSX Continuing Education Committee. We are grateful to Jas for all of her contributions past and those to come.

ISSX is grateful to both Jas and Natalie for their service and commitment to ISSX. Both were awarded their ISSX Service Award during the last in-person meeting of Council in Montreal in July 2018.

Book Reviews HANDBOOK OF DRUG METABOLISM (DRUGS AND THE PHARMACEUTICAL SCIENCES) Editors; PG Pearson, Wienkers LC CRC Press, Taylor & Francis Group: 696pp. ISBN-13: 978-1482262032. 3rd Edition. 2019 As stated by the editors in the preface to the 2nd edition of this book (2008), “the goal of the first edition was to provide a comprehensive text to serve as a graduate course in drug metabolism, a useful reference for academic and industrial drug metabolism scientists, but also to serve as an important reference tool for those pursuing a career in drug metabolism.”

Nearly twenty years have passed since this first edition was published and now a third is available providing testament to the enduring and comprehensive nature of this work. The third edition has been updated to include revised chapters on drug transporters, aspects of metabolic activation, large molecule disposition and stereochemical factors influencing drug metabolism.

The contents are divided into four basic sections; (1) Fundamental aspects of drug metabolism, (2) Factors which affect drug metabolism, (3) Technologies to study drug metabolism, (4) Applications of metabolism studies in drug discovery and development.

If you missed the first two editions now is the chance to acquire this one. If you have any previous edition now is the time to update. An excellent text that is well worth obtaining.

Notified by Steve Mitchell, B.Sc., B.Phil., Ph.D., D.Sc. Faculty of Medicine Imperial College London

ALEXANDER URE AND THE BIRTH OF DRUG METABOLISM Authors; SC Mitchell, RH Waring Printed.com: London 42pp. Monograph. 2018 This short monograph is a timely reminder of the role that Alexander Ure played in the discovery of xenobiotic metabolism. Since both authors have a long association with the city of Birmingham, England, it is apt to quote from another son of the city, J.R.R. Tolkien …“and some things that should not have been forgotten were lost.

History became legend. Legend became myth” (The Fellowship of the Ring, 1954). Regrettably, the part played by Alexander Ure has become obfuscated and almost lost in time. This monograph is like the “Phoenix bird rising from the ashes;” a rebirth for Alexander Ure.

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Reviewed by Glyn B. Steventon, Managing Director, ADMET Solutions Ltd, Basingstoke, UK

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The monograph is superbly written and the referencing was clearly a labour of love in terms of the depth and breath. The tenacity of the authors has to be admired.

The opening paragraphs quickly introduce the fascination of xenobiotic metabolism, from the first anecdotal reports of orally ingested turpentine producing urine that smelt of violets to the wonderful stories of the production of malodourous urine following the consumption of asparagus. This leads the reader on to the history of the conjugation of benzoic acid with the amino acid glycine to form hippuric acid. For those individuals in the field of xenobiotic metabolism what unfolds will be an informative read which redresses the role that Ure played in this discovery. For those with a passing interest, this will be a delightful journey through the mists of time. The detail of the story of the discovery of hippuric acid as a metabolite of benzoic acid is very thorough and extremely well referenced.

The information provided about the life of Alexander Ure is wonderful, the figures and photographs used add to and aid the telling of this fascinating story. For those devotees of xenobiotic metabolism and anyone with an interest in the history of science, they will enjoy reading this monograph.

You’re Invited to Join us for the 12th International Meeting Why You Should Attend the 12th International ISSX Meeting This meeting provides a wonderful opportunity for members of the international scientific community to exchange ideas and expertise, to develop a common vision, and to create and nurture fruitful collaborations in fields related to the study of chemicals that are foreign to the body.

Enjoy state-of-the-art scientific sessions, poster presentations and commercial exhibits in a relaxed and friendly environment. Please take this unique opportunity to expand and share your knowledge on the interaction of foreign chemicals with living systems, renew or develop friendships with your colleagues from around the world, and enjoy everything the wonderful city of Portland has to offer.

Our top five reasons to attend are: 1. L earn the latest information in this dynamic and specialized field through our Short Course program, a variety of timely scientific symposia, and topical keynote and plenary sessions.

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2. E xpand your knowledge of drug metabolism and disposition by learning from our outstanding faculty assembled from leading experts in the field worldwide.

3. G ain recognition and feedback on your research by submitting an abstract and presenting a poster.

All accepted abstracts will be printed in a special supplemental issue of Drug Metabolism and Pharmacogenetics. Students and postdocs may enter the poster competition and compete for prizes and recognition.

4. S cientific meetings organized by ISSX offer numerous outstanding scientific sessions and many opportunities for substantive conversations with scientists worldwide. Our exhibitors will be showcasing the products and services important to you in your research and development.

5. E njoy informal social interactions with fellow researchers, and also enjoy exploring Portland, Oregon!

Preliminary Schedule (Schedule is subject to change)

July 28–Sunday 10:00–13:00 | Concurrent Short Courses 1 and 2 Short Course 1: Advances in the Role of Transporters in Drug Development Chair: Yingying Guo, Eli Lilly and Company, Indianapolis, Indiana, USA The Next Frontier in ADME Research: Predicting and Verifying Tissue Drug Concentrations Using a Proteomics and PET Imaging Approach Jashvant Unadkat, University of Washington, Seattle, Washington, USA Advancing Predictions of Tissue and Intracellular Drug Concentrations Using in vitro and PBPK Modeling Approaches Yingying Guo, Eli Lilly and Company, Indianapolis, Indiana, USA Influence of Transporter Polymorphisms on Drug Disposition and Response: A Perspective from the International Transporter Consortium Sook Wah Yee, University of California San Francisco, San Francisco, California, USA Can BSEP Inhibition Testing in Drug Discovery and Development Reduce Liver Injury Risk? An International Transporter Consortium Perspective Gerry Kenna, Safer Medicines Trust, Kingsbridge, Devon, United Kingdom Transporter DDIs—A Regulatory Perspective “Transporters in Drug Development: Scientific and Regulatory Considerations” Lei Zhang, Silver Spring, Maryland, USA Speaker Panel Discussion

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12th International ISSX Meeting Continued from previous page Short Course 2: Non-P450 Enzymes in ADMET for Drug Discovery and Development Co-Chairs: Cyrus Khojasteh, Genentech, South San Francisco, California, USA, and Kouichi Yoshinari, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan An Overview of Non-P450-mediated Metabolism in Drug Development Cyrus Khojasteh, Genentech, South San Francisco, California, USA Role of Glucuronidation in Drug Metabolism and Toxicity Ryoichi Fujiwara, University of Arkansas, Little Rock, Arkansas, USA Enzymology and Clinical Importance of Reductases and Hydrolases Matt Cerny, Pfizer Inc., Groton, Connecticut, USA Significance of Hydrolases and Aldehyde Oxidase in Drug Toxicity Tatsuki Fukami, Kanazawa University, Kanazawa, Japan 14:00–17:00 | Concurrent Short Courses 3 and 4 Short Course 3: State of the Art PKPD and QSP Modeling Chair: Piet van der Graaf, Certara, Sheffield, United Kingdom, and Marjoleen Nijsen, Abbvie, Chicago, Illinois, USA Introduction to QSP Piet van der Graaf, Certara, Sheffield, United Kingdom Tutorial: How to Build a QSP Model in Less than One Hour Andrzej Kierzek, Certara, Sheffield, United Kingdom Application of QSP in Drug Discovery R. Adam Thompson, Abbvie, Chicago, Illinois, USA

Short Course 4: Idiosyncratic Drug-induced Liver Injury Co-Chairs: Gerry Kenna, Safer Medicines Trust, Kingsbridge, Devon, United Kingdom, and Ann Daly, Newcastle University, Newcastle upon Tyne, United Kingdom

Visit www.issx2019.org/register to take advantage of the early registration discount.

Act fast—advantage pricing ends 31 March!

The Role of Inflammatory Mediators in Idiosyncratic Drug-induced Liver Injury Jack Uetrecht, University of Toronto, Toronto, Ontario, Canada Clinical aspects of Hepatocellular and Cholestatic Drug-induced Liver Injury Einar S. Björnsson, Landspítali - The National University Hospital of Iceland, Reykjavik, Iceland Cellular and Animal Models of Idiosyncratic Drug-induced Liver Injury Tsuyoshi Yokoi, Nagoya University, Nagoya, Japan Progress Made in Understanding Genetically-inherited Susceptibility Factors, Including HLA Genotype Ann Daly, Newcastle University, Newcastle upon Tyne, United Kingdom 18:30–20:30 | Attendee and Exhibitor Meet and Greet

July 29–Monday 07:45–08:45 | New Investigator Session Chair: Bhagwat Prasad, University of Washington, Seattle, Washington, USA All investigators within their first ten years of receiving their highest earned degree are welcome to attend and participate in this session. Continental breakfast will be available to attendees.

07:45–08:45 | Focus Group Session 1: Bioanalysis in ADME Science Chair: Kevin Bateman, Merck and Co-Chair: Jens Sydor, Abbvie

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Therapeutic Area Case Study: QSP in Inflammatory Disease Kapil Gadkar, Genentech, South San Francisco, California, USA

Registration is now open!

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Therapeutic Area Case Study: QSP in Immuno-oncology Shihem Bihorel, University of Florida, Orlando, Florida, USA

REGISTRATION

12th International ISSX Meeting Continued from previous page ABSTRACT SUBMISSIONS Submit an abstract at www.issx2019.org/ abstracts. Present a poster in the general abstract poster sessions. Presentation sessions will be held on Monday, 29 July–Wednesday, 31 July.

Compete in the student poster awards competition—Open to the categories of predoctoral and postdoctoral students, six finalists from each category will be chosen to present their posters. The awards presentation will be held on Wednesday, 31 July.

Before you submit, review the guidelines and ensure that at least one author is a current ISSX member. The deadline for Abstract Poster Presentations submissions and for Predoctoral and Postdoctoral Poster Awards Competition submissions is Sunday, 31 March at 11:59 p.m., Eastern Time (US).

09:00–10:00 | Plenary Lecture: How Technology, Big Data and Systems Approaches are Transforming 21st Century Healthcare Leroy Hood, Providence St. Joseph Health, Renton, Washington, USA 10:00–11:00 | ISSX Membership Meeting ISSX President, Tom Baillie, University of Washington, Seattle, Washington, USA ISSX Members are invited to attend this special member session to learn about Society updates and initiatives.

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13:00–15:00 | Concurrent Sessions Symposia 1 and 2 Symposium 1: Personalized Medicine: Use of Pharmacogenomics and Other Patient-specific Factors to Individualize Drug Dosing and Treatment Co-Chairs: Ann Daly, Newcastle University, Newcastle upon Tyne, United Kingdom, and Tsuyoshi Fukuda, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA Warfarin: A Paradigm for Individualized Dosing Munir Pirmohamed, University of Liverpool, Liverpool, United Kingdom Relevance of Transporter and Metabolic SNPs to Pediatric Treatment Tsuyoshi Fukuda, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA

CPIC Guidelines and Implementation to Date Kelly Caudle, St Jude Children’s Research Hospital, Memphis, Tennessee, USA Personalized Treatment of Cancer Howard McLeod, Moffitt Cancer Center, Tampa, Florida, USA Symposium 2: State of the Art for Organs on Chips Co-Chairs: Edward Kelly, University of Washington, Seattle, Washington, USA, and Roos Masereeuw, Utrecht University, Utrecht, the Netherlands Kidney Organoids for Disease Modeling and High Throughput Screening Benjamin Freedman, University of Washington, Seattle, Washington, USA Lecture Title to be Confirmed Paul Vulto, Mimetas, Lieden, Netherlands "Tissues on Chips"—A Novel Tool for Toxicity and Efficacy Testing on Human Tissue Bo Yeon Lee, NCATS, NIH, Bethesda, Maryland, USA Biofabrication of Liver Constructs for Drug Toxicity Studies Kerstin Schneeberger, Utrecht University, Utrecht, Netherlands 15:30–17:30 | Concurrent Sessions Symposia 3 and 4 Symposium 3: Quantitative Pharmacokinetic and Pharmacology Methods and Strategies in the Discovery and Development of Biotherapeutics Co-Chairs: Hannah Jones, Pfizer Inc., Cambridge, Massachusetts, USA, and Joe Balthasar, University of Buffalo, Buffalo, New York, USA Development and Application of a PBPK Model for Large Molecules in Pfizer Hannah Jones, Pfizer Inc., Cambridge, Massachusetts, USA PBPK and PKPD Modeling to Investigate Engineered Antibodies Tatsuhiko Tachibana, Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan PBPK Models for Predicting Human PK for Monoclonal Antibodies and Other Large Molecule Modalities Iain Gardner, Certara UK Limited (Simcyp Division), Sheffield, United Kingdom Continued on next page

12th International ISSX Meeting Continued from previous page Systems PK/PD Model Informed Discovery and Development of Cancer Immunotherapy Dhaval Shah, University of Buffalo, Buffalo, New York, USA Symposium 4: Microbiome-Environment-Drug Interactions: Emerging Tools and Applications Co-Chairs: Julia Yue Cui, University of Washington, Seattle, Washington, USA and Sumio Ohtsuki, Kumamoto University, Kumamoto, Japan Impact of Intestinal Flora on Host Metabolism of Drug, Sugar, and Lipid Sumio Ohtsuki, Kumamoto University, Kumamoto, Japan Activity-based Profiling of the Microbiome Response to Chemical Exposures Aaron Wright, Pacific Northwest National Laboratory, Richland, Washington, USA

Impact of the Human Gut Microbiome on Drug Disposition Peter Turnbaugh, NCATS, University of California San Francisco, San Francisco, California, USA Developmental Reprogramming of the Gut Microbiota

by Environmental Toxicants Julia Yue Cui, University of Washington, Seattle, Washington, USA 17:30–19:30 | Poster Viewing in Exhibit Hall

July 30–Tuesday 08:00–09:00 | Plenary Lecture: Evaluation of Disease Progression / Drug Effects by Expanding the PK Concept Hiroshi Suzuki, University of Tokyo Hospital, Tokyo, Japan

ISSX AWARDS PROGRAM

Submit a Nomination for the 2019 ISSX Awards by Friday, 5 April Nominations are now being accepted for the following awards to be presented at the 12th International ISSX Meeting in Portland, Oregon. Nominations are due Friday, 5 April. Submit nominations at www.issx.org/ awards/nominations.

The three awards to be presented at the 12th International ISSX Meeting are:

Award winners can reside in the pharmaceutical industry, CROs, regulatory agencies and not-for-profit organizations involved with drug discovery and development. This award is not restricted to any global region.

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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. The award will consist of a plaque or medal, honorarium and travel support and will normally be presented in conjunction with the appropriate

Distinguished Accomplishments in Drug Discovery and Development Award Presented to an individual or to a team employed in an organization involved in drug discovery and/or development. The award will be presented to an individual or team on the basis of: (1) A single high impact scientific accomplishment that dramatically changed practices in the ADME characterization of drugs or drug candidates, or (2) A sustained body of scientific work that shows a high impact on the ADME characterization of drugs.

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The R.T. Williams Distinguished Scientific Achievement Award—Sponsored by Charles Crespi and Family Presented 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 award will consist of a plaque/medal, an honorarium and travel support, and will be presented along with a lecture once every three years in conjunction with the Society's International Meeting.

international meeting. On occasion, one or two outstanding acts of service will justify the award or a long record of many acts of service without any single outstanding act will be recognized. Preferably, however, the recipient should have a record of many accomplishments some of which are major. The award will not be given for future promise, but on the basis of past service. The President-Elect and President of ISSX will be ineligible for the award for five (5) years after their term of office.

12th International ISSX Meeting Continued from previous page 09:00–09:30 | Refreshment Break with Exhibitors and Posters 09:30–11:30 | Concurrent Sessions Symposia 5 and 6 Symposium 5: Disease Effect on Transporter Regulation and Function Co-Chairs: Kathy Giacomini, University of California San Francisco, San Francisco, California, USA and Raymond Evers, Merck & Co. Inc., Kenilworth, New Jersey, USA Proteomics-Based Studies of Disease Effects on the Brain Barrier Transporters Tetsuya Terasaki, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan SLC16A11: From Human Genetics to Novel Mechanisms Underlying Type 2 Diabetes Eitan Hoch, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA Transporters in Polycystic Kidney Disease Kim Brouwer, University of North Carolina Eshelman School of Pharmacy, Chapel Hill, North Carolina, USA Liver Transporter Activity in Patients with Renal Disease Aubrey Stoch, Merck & Co. Inc., Rahway, New Jersey, USA Symposium 6: Advances in the Study of Drug Metabolism Co-Chairs: Iain Martin, Merck & Co. Inc., Boston, Massachusetts, USA and Mitchell E. Taub, Boehringer Ingelheim, Ridgefield, Connecticut, USA Predicting Routes, Sites, and Products of Metabolism Matt Segall, Optibrium, Cambridge, United Kingdom

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Substrate Recognition by Cytochrome P450s Emily Scott, University of Michigan, Ann Arbor, Michigan, USA Application of in silico DMPK in Drug Discovery and Development Fabio Broccatelli, Genentech, South San Francisco, California, USA

EXHIBITION INFORMATION The 12th International Meeting will feature an exhibition showcasing the products and services that researchers need to advance their work.

The exhibition begins with a 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 should download the Exhibitor Prospectus at https://www.issx2019.org/ exhibitissx2019/.

14:00–16:00 | Concurrent Sessions Symposia 7 and 8 Symposium 7: Driving Asia-Inclusive Global Drug Development through Translational Science and Clinical Pharmacology: Towards Enhanced Benefit-Risk and Decreased Access Lag Co-Chairs: Lei Zhang, Silver Spring, Maryland, USA, and Karthik Venkatakrishnan, Takeda Pharmaceuticals International Co., Cambridge, Massachusetts, USA Prediction of Differences in Pharmacokinetics between Chinese, Japanese, and Caucasian Populations—An Update Geoffrey Tucker, University of Sheffield, Sheffield, United Kingdom Transporter Polymorphisms Drive Inter-ethnic Differences in Drug Response Kathy Giacomini, University of California San Francisco, San Francisco, California, USA Enabling Asia-Inclusive Global Drug Development through Quantitative and Translational Science Karthik Venkatakrishnan, Takeda Pharmaceuticals International Co., Cambridge, Massachusetts, USA

Biosynthesis of Drug Candidates and Metabolites Griff Humphreys, Aranmore Pharma Consultants, Lawrenceville, New Jersey, USA

Impact of Racial/Ethnic Differences in Drug Response: Regulatory Perspectives Anuradha Ramamoorthy, U.S. Food and Drug Administration, Silver Spring, Maryland, USA

11:30–14:00 | Lunch with Exhibitors and Poster Presentations

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12th International ISSX Meeting Continued from previous page Symposium 8: State-of-the-Art Approaches in Drug Metabolizing Enzymes and Transporters (DMET) Biomarker Research: Path from Discovery to Validation Co-Chairs: Xiaoyan Chu, Merck & Co. Inc., Rahway, New Jersey, USA, and Hiroyuki Kusuhara, University of Tokyo, Tokyo, Japan Biomarkers for in vivo Assessment of Transporter Function Martin F. Fromm, Friedrich-Alexander-Universität, Erlangen-Nürnberg, Erlangen, Germany

Integrated Quantitative Proteomics and Metabolomics Approach for Discovery and Validation of UGT2B17 Biomarker to Predict Drug Metabolism Bhagwat Prasad, University of Washington, Seattle, Washington, USA 16:30–17:30 | Concurrent ISSX Focus Group Meetings Focus Group Session 2: Biotransformation Mechanisms and Pathways Chair: Amit Kalgutkar, Pfizer and Co-Chair: Valerie Kramlinger, Amgen

Mechanistic Models for Coproporphyrin I and Creatinine as Endogenous Biomarkers for Transporter Drug-Drug Interactions Aleksandra Galetin, University of Manchester, Manchester, United Kingdom

Focus Group Session 3: Modeling & Simulation Chair: Hartmut Derendorf, University of Florida and Co-Chair: Ping Zhao, Bill and Melinda Gates Foundation

Knockout Mice, Transcriptomics and Metabolomics Approach for Discovery of Endogenous Biomarkers for Renal Drug Transporters Sanjay Nigam, University of California San Diego, San Diego, California, USA

18:30–19:30 | Networking Happy Hour at Spirit of 77 sponsored by Frontage Laboratories, Inc. Join fellow attendees for arcade games, craft beers, and cocktails.

17:30–18:30 | Industry-Sponsored Symposia

HOTEL, TRAVEL, AND VISA INFORMATION Hotel Hotel rooms have been blocked at four hotels. You’ll find the best rate at the DoubleTree by Hilton for $209 USD Single/Double. More information can be found at www.issx2019.org/hotels.

Transportation to the Oregon Convention Center The Oregon Convention Center is located at 777 NE Martin Luther King, Jr. Boulevard, Portland, OR 97232.

• J ust eight miles from Portland International Airport (PDX), visitors can access the Oregon Convention Center (OCC) via Interstate 5 North from Exit 302A– Rose Quarter, or from Interstate 84 West Exit 1–Lloyd Boulevard.

Visa For many people, letters of invitation help smooth the visa process and we wish to support international attendees in their efforts to secure the needed travel

ISSX cannot guarantee that you will receive a visa. The decision to grant visas is at the sole discretion of the embassy/consulate. The meeting organizers cannot change the decision of the governmental agency should your application be denied. We are not able to directly contact any government’s visa issuing authority on your behalf. We cannot send letters of invitation via express mail services.

To request a letter of invitation, please email (indicate "invitation letter" in the subject line) ISSX at information@issx.org.

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•P ortland Streetcar’s Central Loop stops at the MLK Lobby entrance every 15 minutes.

We require that you provide your full name, address, and email for us to process the official letter of invitation. The letter of invitation does not financially obligate the ISSX Scientific Meeting organizers in any way. All expenses incurred in relation to the meeting are the sole responsibility of the attendee.

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• Portland’s TriMet MAX light rail stops 300 times a day at the convention center, connecting riders to downtown, surrounding neighborhoods, the Oregon Zoo, and Portland International Airport.

documentation. However, in order to receive a letter of invitation, the meeting organizers must be assured that you intend to attend the meeting if your travel request is granted. Individuals that require an official letter of invitation in order to obtain a visa and authorization to attend the meeting must first register for the meeting and then request a Visa Letter of Invitation.

12th International ISSX Meeting Continued from previous page July 31–Wednessday 09:00–10:00 | Plenary Lecture: Drug Metabolism, Pharmacogenomics and the Quest to Personalize HIV Treatment and Prevention Namandje Bumpus, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA 10:00–10:30 | Refreshment Break with Exhibitors and Posters 10:30–12:30 | Concurrent Sessions Symposia 9 and 10 Symposium 9: Role of Albumin in Drug Disposition Revisited Co-Chairs: Malcolm Rowland, University of Manchester, Manchester, United Kingdom, and Stephen Hall, Eli Lilly and Company, Indianapolis, Indiana, USA Albumin-mediated Hepatic Uptake of Organic Anion Transport Polypeptide Substrates Yuichi Sugiyama, Sugiyama Laboratory, RIKEN Baton Zone Program, RIKEN, Yokohama, Kanagawa, Japan Effects of Albumin on Prediction of Liver Kpuu and Human Hepatic Clearance for Enzyme- and TransporterMediated Mechanisms Li Di, Pfizer Inc., Groton, Connecticut, USA Impact of Albumin and Plasma on the Renal Uptake of OAT1 Substrates Roos Masereeuw, Utrecht University, Utrecht, the Netherlands

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Symposium 10: Ontogeny of Enzymes and Transporters and their Implications in Pediatric PBPK Modeling to Inform Pediatric Dosing Co-Chairs: J. Steven Leeder, Children's Mercy Hospital, Kansas City, Missouri, USA, and Ping Zhao, Bill & Melinda Gates Foundation, Seattle, Washington, USA Ontogeny of Human Membrane Transporters: from Data to Application Saskia de Wildt, Radboud University Medical Center, Nijmegen, Netherlands

Pediatric PBPK: Dealing with Uncertain Parameters and Deciding on Success Criteria for Predictability Trevor Johnson, Certara UK Limited (Simcyp Division), Sheffield, United Kingdom Use of ‘Virtual Children’ to Inform Exposure-Controlled Dosing of Drugs in Children Jean Dinh, Children's Mercy Hospital, Kansas City, Missouri, USA Building, Verifying and Validating Pediatric PBPK Models: Vulnerabilities and Knowledge Deficits Ping Zhao, Bill & Melinda Gates Foundation, Seattle, Washington, USA 12:30–14:30 | Lunch with Exhibitors and Poster Presentations 14:30–16:00 | ISSX Awards Presentations and Lectures Nominate a colleague for an ISSX Award: www.issx.org/awards/nominations 16:00–18:00 | Plenary Symposium 11 Symposium 11: ‘War Stories’—ADME Issues Encountered and Addressed in Drug Discovery and Development Co-Chairs: Marcel Hop, Genentech Inc, South San Francisco, California, USA and Deepak Dalvie, Celgene, San Diego, California, USA Navigating through Clinical Development Painlessly: Snapshots within the Nav1.7 Program Jae Chang, Genentech Inc, South San Francisco, California, USA Elagolix: A Mechanistic Understanding of Drug-Drug Interactions Arian Emami-Riedmaier, Abbvie, Chicago, Illinois, USA ZEPATIER: The Tale of Two Novels Christine Fandozzi, Merck & Co. Inc., USA Management of MIST in a Case of Multiple Metabolic Species Differences Lars Weidolf, AstraZeneca, Mölndal, Sweden 18:00–18:30 | Closing Session

ISSX THANKS THESE MEETING SPONSORS FOR THEIR SUPPORT:

Become an ISSX Membership Ambassador As a member of the Society, you know your connection to peers in the industry, access to industry news and resources, and admission to educational events are of great value for you and your professional and personal development.

Becoming an ISSX Membership Ambassador is as simple as following these five steps:

Perhaps you have been looking for a way to inform your peers about how ISSX has helped you grow professionally or how your research has benefited from your membership.

2. Use this guide and the enclosed materials to inform your network of peers and colleagues about why you are a member of ISSX and why they should join.

Now you can!

ISSX has launched a Membership Ambassador Program to share information about the benefits of being part of the Society.

1. Sign up for the program online at www.issx.org/ambassador.

3. Ask your colleague to list you as their ISSX member contact when they join at www.issx.org/join or send a direct link to join from your membership. This will ensure you receive credit for their new membership.

4. Follow up with your colleague after they join to ensure they are aware of the resources available to them as a newly minted member of ISSX. 5. Share your success with us! You could be a featured ISSX Membership Ambassador in an upcoming issue of the ISSX Newsletter! Tell us about your recruitment efforts and we will spotlight your accomplishments.

REFER NEW MEMBERS BY EMAIL Find Your Link 1. Login to your ISSX Membership Account at www.issx.org.

Send Your Invitations 1. Use the referral form to send invitations to up to ten colleagues or,

2. Select the link to “My Profile”

2. Copy your referral link and send invitations directly to your network

3. Select the link to “Refer a Friend”

/ISSX Newsletter / 11

Learn more online and volunteer for this program at www.issx.org/ambassador.

Issue 1, 2019

ISSX will feature ambassadors in the ISSX Newsletter and in our social media outreach. To ensure you will be featured, be sure to sign up to become an ambassador between now and April 1, 2019.

President’s Message Continued from page 1 put in place an outstanding scientific program, and given the attractive venue of the Pacific NW at the height of the summer, this should be a popular and highly successful event. Registration for the Portland meeting is now open and can be accessed via the Society website.

Dhaval Shah (SUNY Buffalo) and Honghui Zhou (J&J).

Special thanks to Nancy Agrawal and Ian Knemeyer of Merck for securing this excellent venue for the workshop!

Please mark your calendars for what promises to be a very popular educational activity.

Although only one meeting is planned for this year, I am pleased to announce that ISSX will be sponsoring a workshop in December 2019, the topic of which is, “Disposition of Biologics,” a subject of growing importance in both academia and the biotech/ pharmaceutical industries. The workshop, which will take place on December 12–13, 2019, at the Merck Research Laboratories facility in Boston, MA, is being organized by

As always, comments and suggestions as to how ISSX can continue to best serve the needs of its members are encouraged and much appreciated.

Sincerely, Tom Baillie President, ISSX

Be a Part of the ISSX Mentorship Program this Year

12

/ISSX Newsletter / Issue 1, 2019

Learning, growing, guiding, and giving back. These are all benefits associated with the ISSX Mentorship Program, powered by MentorcliQ- a fast and user-friendly cloud-based mentoring platform.

A complimentary benefit exclusively for members of ISSX, the ISSX Mentorship Program provides a rich opportunity for graduate students and newer investigators to be matched with more senior scientists within and across career pathways to discuss career options, review competencies for success, consider challenges and problems, and receive practical advice from experienced scientists.

For the second mentoring cycle ISSX will be allowing mentors and mentees to enroll on an ongoing basis, both prospective mentors and mentees will create a custom profile in the ISSX MentorcliQ portal and the system will then use a Nobel Prize-winning algorithm to evaluate all possible matches and optimize matches across the entire pool. Individuals then develop their mentoring relationships and work together to achieve mentoring goals. The mentoring portal provides the right structure, support, and guidance to help these relationships succeed. ISSX provides the mechanism, checkpoints, templates, logs, midpoint review tools, and more.

Follow this link to join the ISSX Mentorship Program: www.issx.org/ISSXMentorship Mentoring is a personal and professional development experience that challenges one to reflect on their own actions and behaviors over time. For those who have benefited from a helpful mentor in their lives or careers, there is often a strong drive to pay this forward to others by serving in the same role. The act of helping someone develop, grow, and navigate life and career obstacles is incredibly rewarding.

Launched in 2018, this program has already connected a number of mentors and mentees for rewarding mentoring experiences.

Finding a true mentor is not always easy. The ISSX Mentorship Program can help and we are proud to offer this valuable resource and opportunity for new relationships to begin.

Welcome New Members The International Society for the Study of Xenobiotics proudly welcomes the following new members. We greatly appreciate their support and hope that each remains aligned and affiliated with ISSX for many years to come.

Marysol Almestica-Roberts, United States

Robert Jones, United States

Jelle Reinen, Netherlands

Kendan Jones-Isaac, United States

Hong Ren, China

Herve Aloysius, United States

Keith Kennedy, United States

Yuanyuan Shi, United States

Kavya Annu, United States

Amanda King-Ahmad, United States

Ryota Shizu, Japan

Yifan Bao, United States

Hong-zhen Li, China

Sheri Smith, United States

Kyoungju Choi, United States

Shuaibing Liu, China

James Stygall, United Kingdom

Cleavon Cloete, South Africa

Ying-yun Lu, China

Disha Thakkar, India

Collet Dandara, South Africa

Riyazuddin Mohammed, India

Larry Tremaine, United States

Xiao-na Dong, China

Parusharamulu Molgara, India

Pei Wang, China

Basma ElBakary, United Kingdom

Julie Murrell, United States

Mandy Xu, China

Jing-kai Gu, China

Boonsri Ongpipattanakul, Thailand

Sheng-ju Yin, China

Xing Jie, China

Mustafizur Rahman, Bangladesh

Junjie Zhu, United States

Joshua Johnson, United States

Save the Date!

Disposition of Biologics

/ISSX Newsletter / 13

Mark your calendars now and be one of the first to register to attend when registration opens this spring!

Issue 1, 2019

This December 12–13, ISSX will host the workshop “Disposition of Biologics” at Merck Research Laboratories in Boston, Massachusetts, USA.

/ISSX Newsletter / Issue 1, 2019 14

The 21st International Conference on Cytochrome P450 (ICCP450) organizing committee invites you to participate in the 2019 International Conference to be held from Sunday 23–Thursday 27 June 2019 at The University of Queensland, Brisbane, Australia.

The conference programme will consist of a rich schedule of presentations at the forefront of P450 research featuring their roles in the metabolism of drugs and other xenobiotics:

Join us in Brisbane, Australia's only sub-tropical capital city, with a perfect climate for international visitors.

A sophisticated and multicultural city with a relaxed lifestyle, Brisbane hosts world-class museums, art galleries, performance venues and universities, and internationally recognized research institutes and hospitals. It is an ideal base for exploring some of the great attractions that Australia and New Zealand have to offer. The timing of ICCP450 2019 at the start of the northern summer provides a perfect opportunity to extend your trip ‘down under’ to enjoy some sightseeing.

Brisbane is a short drive to the beaches of the Gold and

Sunshine Coasts, or to the rainforest in local national parks. It’s also just a short flight to the World Heritagelisted Great Barrier Reef, Uluru, Sydney with its iconic Opera House, cosmopolitan Melbourne and the wineries around Adelaide.

For updates about the scientific program and all conference related information please visit the conference website at www.iccp450brisbane.com or contact the conference secretariat, Expert Events at iccp450@expertevents.com.au.

Header 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.org/advertising or contact Scott Narug at snarug@issx.org.

Editor Dr. Allen Cato, III Cato Research, LTD 6480 Weathers Place, Suite 104 San Diego, California 92121 USA Telephone: +1-858-452-7271 Fax: +1-858-452-7784 E-mail: jcato@cato.com

Change of Address

If 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 website. 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 Scott Narug at snarug@issx.org.