ISSX Newsletter | Issue 2, 2019

Volume 42

Issue 2, 2019

ISSX President’s Message

By Thomas Baillie, ISSX President As I write this brief President’s Message, we are rapidly approaching the Society’s premier event of 2019, namely the 12th International ISSX Meeting, scheduled to take place in Por tland, Oregon, from July 28–31.

As you will read elsewhere in this newsletter, the meeting co-chairs, Aleksandra Galetin, Deepak Dalvie, and Hiroyuki Kusuhara, together with their Meeting Organizing Committee, have put in place an exciting scientific program that encompasses key topics ranging from basic scientific advances in xenobiotic metabolism and disposition to applications of new approaches to the discover y, development, and regulator y approval of novel therapeutic agents. Meeting registration is proceeding at a brisk pace and, at the time of writing, is well ahead of that for the 2017 conference in Providence, Rhode Island, as well as last year’s meeting in Montreal, Canada, both of which attracted over 600 attendees. The

12th International ISSX Meeting thus promises to be an event not to be missed, and if you have not yet registered, I would encourage you to do so soon.

Planning is also well under way for the ISSX Workshop on “Disposition of Biologics,” to be held in Boston, Massachusetts, on December 12–13, 2019. You will find preliminar y details of the event in this newsletter, and the full program with online registration will be posted on the ISSX website in due course. It is our intent to host a workshop focused on contemporar y issues in our field each year, and a number of topics are currently under consideration for 2020 and beyond.

Finally, I am happy to repor t that the ISSX Mentoring Program, introduced last year as a free benefit to ISSX members in the early stages of their careers, is now in its second six-

month cycle with 41 par ticipants enrolled.

Feedback from the inaugural offering of this program was highly positive and it is Thomas Baillie, Ph.D. gratifying to ISSX President. see the level of engagement of senior members of the Society who are “giving back” to our discipline through their ser vice as mentors.

As always, I welcome comments and suggestions as to how ISSX can continue to best ser ve the needs of its membership. I hope to see many of you at the meeting in Por tland at the end of July.

Sincerely, Tom Baillie President, ISSX

IN THIS ISSUE 2

Book Review

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Why You Should Attend The 12th International ISSX Meeting

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Welcome New ISSX Members ISSX Workshop: Disposition of Biologics

an ISSX Membership 11 Become Ambassador

Book Review HANDBOOK OF SOLVENTS Volume 2: (3rd edition). Use, Health, and Environment.

Editor: G. Wypych ChemTec Publishing, Toronto, Canada Pages 942. ISBN: 978-1-92788-542-0. 2019 Amidst the publicity for this third edition is the statement that this volume “contains the most comprehensive information ever published on solvents.”

It is cer tainly a tour de force and an update, revision and expansion of the previous editions. Perhaps most impor tantly for ISSX members are the sections concerning the toxicity and biological interactions of these chemicals. With a few exceptions, it is difficult to assess the potential toxicity of solvents, especially when individuals are subjected to low levels or mixtures over shor t periods. Classic examples of industrial exposure are covered and assessments of low-level contact provided. This is all placed in the context of solvent usage and the text, “provides essential best practice guidance for human health considerations.”

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The text is divided into the following sections, the titles of which are given below, and each of these sections is subdivided into many segments. “Solvent use in various industries,” “Methods of solvent detection and testing,” “Residual solvents in products,” “Environmental impact

of solvents,” “Concentration of solvents in various industrial environments,” “Regulations,” “Toxic effects of solvent exposure,” “Substitution of solvents by safer products,” “Solvent recycling, removal and degradation,” “Natural attenuation of chlorinated solvents in ground water.”

A nine page contents and a for ty-nine page index provide copious cross referencing and the ability to find exactly what one is looking for in this comprehensive text. The book is well made, strong covers, good quality paper, and easy-to-read print. It should last through many consultations and usage in the laborator y setting.

Reviewed by

Steve Mitchell Faculty of Medicine Imperial College London London SW7 2AZ, UK

Book Ordering Information Chem Tec Publishing (via Elsevier) 38 Earswick Drive, Toronto Ontario M1E 1C6 Canada

Why You Should Attend the 12th International Meeting The 12th International ISSX Meeting will bring together internationally renowned scientists and young scientists from academia and industr y working on drug/ xenobiotic research in diverse fields including basic and clinical pharmacology and therapeutics, toxicology, oncology, endocrinology, physiology, biochemistr y, medicinal chemistr y, molecular and structural biology and genetics.

Attendees will enjoy state-of-the-ar t scientific sessions, poster presentations, and commercial exhibits in a relaxed and friendly environment. Please take this unique oppor tunity 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 ever ything the wonder ful city of Por tland has to offer.

Top Five Reasons to Attend the 12th International ISSX Meeting: 1. L earn the latest information in this dynamic and specialized field through our shor t course program, a variety of timely scientific symposia, and topical keynote and plenar y sessions.

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

3. V iew the latest research and talk with abstract authors during the poster presentations. All accepted abstracts will be printed in a special supplemental issue of Drug Metabolism and Pharmacokinetics.

Dr. Lawrence J. Lesko is currently Emeritus Professor and Founding Director of the Center for Pharmacometrics and Systems Pharmacology at the University of Florida (UF) College of Pharmacy at Lake Nona (Orlando). He star ted the Center in 2011 and ser ved as its full-time Director for five years. He continues par t-time in the Center and officially retired from UF in Februar y 2018. He now ser ves as a consultant to pharmaceutical companies and as a strategic advisor y board member of several biosimulation, genomic and healthcare organizations.

In 1995, Dr. Lesko became the first Director of the Office of Clinical Pharmacology (OCP) in the Center for Drug Evaluation and Research at the Food and Drug Administration. His tenure as Office Director was for 16 years until his retirement in 2011. At the FDA, Dr. Lesko formed a pharmacological mechanism-based drug safety assessment team to analyze the root cause of adverse drug events. This program used mechanistic approaches to understand off-target drug effects using bioinformatics strategies. He also led the advancement of precision medicine through the update of labels of previously approved drugs with new genetic information on safety, dosing and efficacy.

Dr. Lesko has coauthored numerous Guidances for Industr y including “Clinical Pharmacogenomics: Premarketing Evaluation in Early Clinical Trials� and “Pharmacogenomics Data Submissions." He also star ted a Division of Pharmacometrics (i.e., Biosimulation) that is responsible for quantitative analysis of dose response, PBPK and PK-PD (biomarkers) relationships to suppor t optimal dosing in FDA approved drug labels, and the development of drug-disease models to suppor t clinical trial simulations in drug development. Dr. Lesko has published more

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

Lawrence J. Lesko to present ModelInformed Precision Dosing at the Bedside: Scientific Challenges and Opportunities on Sunday, 28 July.

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4. V isit with more than for ty exhibitors who will be showcasing products and ser vices impor tant to you in your research and development.

Keynote Speaker

12th International ISSX Meeting Continued from previous page than 225 peer-reviewed manuscripts and is a frequent invited national and international speaker.

Dr. Lesko was admitted as a Fellow in the College of Physicians of Philadelphia in 2019. In 2018, Dr. Lesko received the first FDA OCP Distinguished Alumni Lectureship Award for his contributions to clinical pharmacology. Dr. Lesko also received the prestigious UF Global Gator Award in 2017 for his contributions to international drug development. He was the recipient of the 2015 Leadership Award from the International Society of Pharmacometrics, the 2015 Agilent Technologies Thought Leader Award in Integrated Systems Toxicology and the 2014 AAPS Distinction in Biomarker Research Award. In 2011, he received the Gar y Neil Prize for Innovation in Drug Development from the American Society of Clinical Pharmacology and Therapeutics (ASCPT). Dr. Lesko also was honored with the Rawls Palmer Progress in Medicine award from ASCPT, the Coriell Scientific Leadership Award for Personalized Medicine, the University of Nor th Carolina Institute for Pharmacogenomics and Individualized Therapy Award for Clinical Ser vice, and the Nathanial B. Kwit Distinguished Ser vice Award for Clinical Pharmacology from the American College of Clinical Pharmacology.

Visit www.issx2019.org/register to secure your seat at the meeting.

Short Course 4: Idiosyncratic Drug-induced Liver Injury Co-Chairs: Gerr y Kenna, Safer Medicines Trust, Kingsbridge, Devon, United Kingdom, and Ann Daly, Newcastle University, Newcastle upon Tyne, United Kingdom 17:30–17:40 | Meeting Opening and Welcome 17:40–18:30 | Keynote Lecture: Model-Informed Precision Dosing at the Bedside: Scientific Challenges and Opportunities Lawrence Lesko, Emeritus Professor, University of Florida, Orlando, Florida, USA 18:30–20:30 | Attendee and Exhibitor Meet and Greet Sponsored by

29 JULY–MONDAY

Visit www.issx2019.org/program to view the program and speaker details.

07:45–08:45 | Concurrent Sessions: New Investigator Session and Focus Group Session

28 JULY–SUNDAY

New Investigator Session Chair: Bhagwat Prasad, University of Washington, Seattle, Washington, USA

Short Course 1: Advances in the Role of Transporters in Drug Development Chair: Yingying Guo, Eli Lilly and Company, Indianapolis, Indiana, USA

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Registration is open!

ISSX2019 Schedule-at-a-Glance

10:00–13:00 | Concurrent Short Courses 1 and 2

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REGISTRATION

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 14:00–17:00 | Concurrent Short Courses 3 and 4 Short Course 3: State of the Art PKPD and QSP Modeling Co-Chairs: Piet van der Graaf, Cer tara, Sheffield, United Kingdom, and Marjoleen Nijsen, Abbvie, Chicago, Illinois, USA

Focus Group Session 1: Bioanalysis in ADME Science Chair: Kevin Bateman, Merck and Co-Chair: Jens Sydor, Abbvie 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 11:00–13:00 | Lunch Break, Visit Exhibitors, and Poster Presentation

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12th International ISSX Meeting Continued from previous page 11:00–13:00 Poster Presentations Sponsored by

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 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

Symposium 6: Advances in the Study of Drug Metabolism Co-Chairs: Iain Mar tin, Merck & Co. Inc., Boston, Massachusetts, USA and Mitchell E. Taub, Boehringer Ingelheim, Ridgefield, Connecticut, USA 11:30–14:00 | Lunch Break, Visit Exhibitors, Poster Presentations, and Exhibitor Showcase 11:30–14:00 Poster Presentations Sponsored by

12:30–13:00 Exhibitor Showcase Sponsored by

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 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 17:30–19:30 | Poster Viewing in Exhibit Hall

30 JULY–TUESDAY

09:30–11:30 | Concurrent Sessions: Symposia 5 and 6

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 16:00–16:30 | Refreshment Break with Exhibitors and Posters Exhibitor Showcase Sponsored by

16:30–17:30 | Concurrent Sessions: ISSX Focus Group Meetings

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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., Kenilwor th, New Jersey, USA

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, Mar yland, USA and Kar thik Venkatakrishnan, Takeda Pharmaceuticals International Co., Cambridge, Massachusetts, USA

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

14:00–16:00 | Concurrent Sessions: Symposia 7 and 8

12th International ISSX Meeting Continued from previous page Focus Group Session 2: Biotransformation Mechanisms and Pathways Chair: Amit Kalgutkar, Pfizer and Co-Chair: Valerie Kramlinger, Amgen Focus Group Session 3: Modeling & Simulation Chair: Har tmut Derendor f, University of Florida and Co-Chair: Ping Zhao, Bill and Melinda Gates Foundation

12:30–14:30 | Lunch Break, Visit Exhibitors, Poster Presentations, and Exhibitor Showcase 12:30–14:30 Poster Presentations Sponsored by

13:15–13:45 Exhibitor Showcase Sponsored by

17:30–18:30 | Industry-Sponsored Symposia (ISS) MilliporeSigma ISS: Tapping the Potential of Gene Editing Technology to Improve Cell-Based Assays for Drug Disposition and Transporter-Mediated Drug-Drug Interactions

David Thompson Ph.D., Sr R&D Manager, In Vitro Safety Systems, MilliporeSigma BioIVT ISS: Potential Benefits of a PhysiologicallyRelevant Whole Cell Model to Assess CYP Inhibition with Complex Mixtures

Amy L. Roe, Ph.D., DABT 18:30–19:30 | Networking Happy Hour at Spirit of 77 Sponsored by

31 JULY–WEDNESDAY 09:00–10:00 | Plenary Lecture: Drug Metabolism, Pharmacogenomics and the Quest to Personalize HIV Treatment and Prevention Namandjé Bumpus, Johns Hopkins University School of Medicine, Baltimore, Mar yland, USA

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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 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

14:30–16:00 | ISSX Awards Presentations and Lectures 16:00–18:00 | 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 18:00–18:30 | Closing Session

1 AUGUST–THURSDAY The 12th International ISSX Meeting will officially conclude on Wednesday, 31 July. Though the meeting will be over, we invite you to stay through Friday and spend Thursday on a tour of the region or a winer y tour.

These tours are available to ISSX attendees at a special rate. Visit the meeting website to reser ve a seat.

09:00–17:30 | ISSX Mt. Hood Loop Tour including Multnomah Falls 10:00–14:30 | ISSX Afternoon Escape to Oregon Wine Country

VISIT THE ISSX BOOTH! This year’s meeting will include an area in the exhibit hall exclusively for ISSX members. A comfor table seating and relaxing area will be available inside the exhibit hall where you can rest, chat with peers, and learn more about ISSX from volunteer leaders.

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12th International ISSX Meeting Continued from previous page Explore Portland Oregon after the Meeting You are invited to stay through Friday and spend Thursday on a tour of the region or a winer y tour. These tours are available to ISSX attendees at a special rate. Visit the meeting website to reser ve a seat.

Mt. Hood Loop Tour If you are searching for the best day tour from Por tland, Oregon, look no fur ther. The Mt. Hood Loop tour offers a fun and stress-free way to see the top sites near Por tland, including the nationally recognized Multnomah Falls and the Columbia River Gorge, Hood River Valley, and Timberline Lodge at Mt. Hood.

Tour Price: $105 per person. Includes transpor tation, visits to three wineries, tasting fees and food pairings at wineries. Guide gratuity is not included but always appreciated.

Price includes: Guest pick up and drop off, transpor tation and tour guide, and all applicable fees, unless other wise stated, are included.

Price does not include: Gratuity and lunch are not included. You will have an oppor tunity to purchase lunch and/or snacks along the way.

Escape to Oregon Wine Country After the ISSX Meeting concludes, join us for an outing to Oregon’s nearby wine countr y.

We’ll take the scenic way into wine countr y and visit a progression of three boutique wineries where you’ll have the oppor tunity to taste and procure wines not available elsewhere. During the day, our guides will host you, sharing information about our wine countr y and we’ll be pairing food to wine at the wineries, so no need to bring a lunch.

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Price includes: Transpor tation, visits to three wineries, tasting fees and food pairings at wineries.

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Price: $125 per person.

12th International ISSX Meeting Continued from previous page Hotel, Travel, and Visa

and then request a Visa Letter of Invitation.

Hotel rooms have been reser ved 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.

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.

Transportation to the Oregon Convention Center The Oregon Convention Center is located at 777 NE Mar tin Luther King, Jr. Boulevard, Por tland, OR 97232.

• J ust 8 miles from Portland International Airport (PDX), visitors can access the Oregon Convention Center (OCC) via Interstate 5 Nor th from Exit 302A–Rose Quar ter, or from Interstate 84 West Exit 1–Lloyd Boulevard.

• Por tland’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.

• Portland Streetcar’s Central Loop stops at the MLK Lobby entrance ever y 15 minutes.

Visa Letters For many people, letters of invitation help smooth the visa process and we wish to suppor t international attendees in their effor ts to secure the needed travel 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

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 ser vices.

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

Exhibition Information The 12th International Meeting will feature an exhibition showcasing the products and ser vices 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 adver tising should download the Exhibitor Prospectus at www.issx2019.org/exhibitissx2019.

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ISSX Thanks These Meeting Sponsors for Their Support:

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

Patrick Allard, UCLA, United States Nathan Anderson, Waters Corporation, United States Joseph Antoun, Biopredic International, United States Pushpa Chandrasekar, Allergan, United States Helene Chapy, UCB Biopharma Sprl, Belgium

Hossein Eslami Amirabadi, Utrecht University, the Netherlands Michael Espiritu, Pacific University, United States Zsuzsanna Gaborik, Solvo Biotechnology, Hungar y Elaine Ginn, Arcus Biosciences, United States

Marina Kubekina, Institute of Gene Biology Russian Academy of Sciences, Russia David Kuninger, Thermo Fisher Scientific, United States Philip Lazarus, Washington State University, United States Jacqueline Leow, Singapore

Richard Gregor y, GSK, United Kingdom

Jing Lin, Qilu Regor Therapeutics, China

Chunyan Han, Pharmaron, China

Kai Liu, Retrophin, United States

Douglas Clarke, University of Huddersfield, United Kingdom

Meng Huang, Enanta Pharmaceuticals, Inc., United States

Elisabeth Lonie, Ironwood Pharmaceuticals, United States

Kate Comstock, Thermo Fisher Scientific, United States

Katja Jansen, Utrecht University, the Netherlands

Ray Cooke, Pharmaron UK Ltd, United Kingdom

Rencong Jiang, Gilead Sciences, United States

Michael Malfatti, Lawrence Livermore National Laborator y, United States

Lindsay Czuba, University of Washington, United States

Helinä Kahma, Finland

Toru Maruyama, Faculty of Pharmaceutical Science, Kumamoto University, Japan

Mar y Davis, United States

Shunsuke Kamigaso, Taisho Pharmaceutical, Japan

Yusuke Masuo, Kanazawa University, Japan

Sayaka Deguchi, Osaka University, Japan

Yusuke Kamiya, Showa Pharmaceutical University, Japan

James McKim, Iontox, United States

Joseph Dempsey, University of Washington, United States

Matt Karasu, University of Washington, United States

Jules Desmeules, Geneva University Hospitals, Switzerland

Takumi Kawanishi, Japan

Cheng Shoong Chong, Bioinformatics Institute, Singapore

Stephen Dueker, Biocore, South Korea

George Eriyamremu, University of Benin, Nigeria

Eunjeong Kim, Handok Inc., South Korea Ayaka Kojima, Meijo University, Japan Kristyna Krasulova, Palacky University Olomouc, Faculty of Science, Czech Republic

Tadahaya Mizuno, University of Tokyo, Japan Russell Mor tishire-Smith, Waters, United Kingdom Darren Moss, Janssen Pharmaceutica, Belgium Continued on page 12

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Ruchia Duggal, Merck & Co., United States

Gaurab Kc, NIBR, United States

Yuu Miyauchi, Kyushu University, Japan Issue 2, 2019

Yanhua Ding, China

Brandon Miller, Key Corporate Ser vices, United States

ISSX WORKSHOP:

Disposition of Biologics December 12–13, 2019 • Merck Research Laboratories, Boston, MA Premier Sponsor

About the Workshop Biologics have become an impor tant and rapidly growing component of modern medicine, which has fundamentally altered the treatment paradigm for many diseases. This class of drug molecules involve myriad biotechnology products ranging from therapeutic proteins (such as monoclonal antibodies, fusion proteins, antibody-drug conjugates) to peptides, vaccines, oligonucleotides, and gene and cell therapies.

While biologics provide an unprecedented oppor tunity to treat, diagnose, and prevent many health problems, they also present unprecedented challenges to drug discover y and development scientists.

One of the key challenges is fundamentally different absorption, distribution, metabolism, and excretion (ADME) behavior of biologics compared to traditional small molecules. In fact, the disposition of biologics is not only unique, many determinants responsible for the pharmacokinetics (PK) of biologics are not yet known.

Consequently, most of the discover y and development effor ts are empirical at present, and disposition behavior of biologics is largely not elucidated when advancing these molecules to preclinical or clinical stages.

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This workshop is designed to help biopharmaceutical scientists overcome this knowledge-gap via educational and state-of-the-ar t presentations and case-studies from world-renowned exper ts in the field.

The Major Goals of This Workshop Are: • T o educate scientists on basic principles and key determinants for the disposition of clinically advanced biologics (e.g., monoclonal antibodies, antibody-drug conjugates, bi-specific antibodies, engineered T-cells, etc.)

• T o demonstrate how the knowledge of disposition helps in the design and optimization, development, clinical translation, and regulator y filing of biologics • T o introduce disposition characteristics of futuristic biologics (viral vectors, oncolytic virus, oligonucleotide, engineered immune cells, etc.)

Who Should Attend?

Biopharmaceutical scientists in industr y, academia, and non-profit organizations who are involved in or interested in the discover y and development of novel biologics should plan to attend this work shop to discover: •K ey determinants responsible for whole-body and tissue-specific disposition of different biologics •H ow biophysical characteristics like size, charge, and glycosylation affect disposition of biologics • T he effect of target engagement on the disposition and toxicity of biologics •H ow to determine optimal dosing regimen for biologics with nonlinear pharmacokinetics • T he impact of immunogenicity on the disposition, efficacy, and toxicity of biologics •D rug-interaction potential of biologics and assessment strategy •W hich biological modality to choose to maximize the probability of clinical success •H ow to employ the knowledge about disposition of biologics to suppor t the discover y, development, clinical translational, and regulator y filing of biologics How Will I Benefit from Attending?

Through the attendance and par ticipation in this workshop, scientists will: • L earn how to assess and characterize disposition profiles of biologics • L earn how to a priori predict the disposition of biologics •U nderstand how quantitative methods such as PK/PD Modeling and Simulation and Quantitative Systems Pharmacology are used to suppor t the discover y and development of biologics

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Become an ISSX Membership Ambassador We hope you'll agree that ISSX is your connection to your peers worldwide, to the latest research discoveries, and to the leading scientific meetings and workshops in the areas related to xenobiotic metabolism.

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. Now you can!

Demonstrate your continued suppor t and commitment to the premier scientific organization for researchers interested in the metabolism and disposition of xenobiotics by becoming an ISSX Membership Ambassador.

What is the ISSX Membership Ambassador Program?

The ISSX Membership Ambassador Program is a volunteer activity developed to help increase awareness and understanding of the value of membership in the Society and to more broadly engage new ISSX members in the various activities we offer.

Why should I become an ISSX Membership Ambassador?

For those who have benefited from the education, fellowship, and the oppor tunity to ser ve on a committee, giving back to others by sharing from your experiences

and identifying paths for new members is a wonder ful oppor tunity to develop personally and to make new friends.

How do I become an ISSX Membership Ambassador?

Becoming an ISSX Membership Ambassador is as simple as following these five steps: 1. S ign up for the program online at www.issx.org/ ambassador.

2. U se 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.

3. A sk your colleagues 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. F ollow up with your colleagues after they join to ensure they are aware of the resources available to them as a newly minted member of ISSX. 5. S hare 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 effor ts and we will spotlight your accomplishments.

REFER NEW MEMBERS BY EMAIL Send Your Invitations 1. U se the referral form to send invitations to up to ten colleagues or,

2. Select the link to “My Profile”

2. C opy your referral link and send invitations directly to your network

3. Select the link to “Refer a Friend”

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

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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!

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Find Your Link 1. L ogin to your ISSX Membership Account at www.issx.org.

Welcome New Members Continued from page 9

Quyen Nguyen, Ipsen Innovation, France

Sara Shum, University of Washington, United States

Deqing Xiao, Gilead Sciences, Inc., United States

James Nguyen, Washington State University, United States

Kyung Yeon Song, Pharmacyclics, United States

Libin Xu, University of Washington, United States

Congrong Niu, Gilead, United States

Lianne Stevens, LUMC, the Netherlands

King Yabut, University of Washington, United States

Timothy Strelevitz, Pfizer Inc., United States

Yoshiaki Yamagishi, Musashino University, Japan

Hailing Sun, Gilead Science, United States

Xin Yang, Pfizer Inc., United States

Whitney Nolte, Children's Mercy Hospital, United States Cindy Obringer, Procter & Gamble, United States Chuong Pham, Alliance Pharma, Inc., United States Rani Qasem, King Saud Bin Abdul Aziz University for Health Sciences, Saudi Arabia Tianjing Ren, The Chinese University of Hong Kong Ar thur Rober ts, University of Georgia, United States Leigh Ann Saucier, Aegis Sciences Corporation, United States

Kazuo Takayama, Osaka University, Japan Daniel Tatosian, Merck & Co., United States Barbora Vyhlidalova, Palacky University, Faculty of Science, Czech Republic

Xinning Yang, Food And Drug Administration, United States Woo Hyun Yoon, Pharmacyclics, United States Rena Zhang, Merck & Co., United States Yuechao Zhao, Enanta, United States

David Wagner, Abbvie, United States Lydia Wang-Lakshman, Novar tis, United States

Disposition of Biologics

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Continued from page 10

•B ecome acquainted with case-studies that can be leveraged to help ongoing or future projects in their organization •G ain insights into futuristic biologics that may become par t of their organization’s por tfolio going for ward •N etwork with other scientists and world-renowned exper ts who are working with similar biologics

Registration opens this summer. Watch for more announcements as the faculty members are confirmed.

We look for ward to seeing you in Boston in December.

Header ISSX Newsletter is published quar terly in the spring, summer, autumn, and winter. For information concerning adver tising 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 director y, 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.