ISSX Newsletter | Issue 4, 2016

Volume 39

Issue 4, 2016

ISSX President’s Message

By Geoff Tucker, ISSX President At the time of writing, I have just returned from the annual meeting of the Japanese Society for the Study of Xenobiotics (JSSX) in Matsumoto, Japan, celebrating its foundation 30 years ago—five years after that of ISSX. The meeting, chaired by Professor Shigeru Ohmori from the Department of Pharmacy at Shinshu University Hospital, featured an outstanding program showcasing the seminal contributions of Japanese scientists to our understanding of drug metabolism and transport.

Professor Allan Rettie of the University of Washington gave a distinguished lecture on the clinical relevance of CYP4 family enzymes, and I reviewed the historical relationship between JSSX and ISSX and outlined some of the new strategic initiatives of ISSX. ISSX has also celebrated the recent success of the ISSX Workshop: Translating Preclinical Data to Human Clearance and Pharmacokinetics, held in Boston,

MA, USA, October 27–28, 2016. The meeting was well-attended with more than 200 attendees and 33 poster abstracts, and featured several scientific sessions that provided fundamental knowledge on current approaches, examined the utility of in vitro and in vivo experimental systems, discussed modeling approaches in human PK/clearance prediction, focused on the current challenges, and offered next steps.

I am pleased to report that ISSX Council has agreed to renew the contract with Taylor & Francis to continue with Drug Metabolism Reviews as the official journal of ISSX. However, the abstracts of all future ISSX meetings will be published in Drug Metabolism and Pharmacokinetics, the official journal of JSSX. The establishment of ISSX Focus Groups is now well advanced, and I am happy to announce the names of the individuals who have kindly

agreed to serve as chairs and co-chairs of the groups. Amit Kalgutkar (Pfizer, USA) and Barry Jones (AstraZeneca, UK) will Geoff Tucker, Ph.D. serve the ISSX President.

Biotransformation Mechanisms & Pathways group; Hartmut Derendorf (University of Florida, USA) and Yusuke Tanigawara (Keio University, Japan) will serve the Modelling & Simulation group; and Mingshe Zhu (BMS, USA) and Kevin Bateman (Merck, USA) will serve the Bioanalysis in ADME Science group. Refer to p. 12 for additional information on how these Focus Groups will function in providing a forum for greater member benefit.

The ISSX webinar series is now in full swing. Dr. Yuchi Sugiyama Continued on next page

IN THIS ISSUE 3 4 5

Book Review ISSX Welcomes New Members New Investigator Spotlight

7 9 10

ISSX Workshop in Review Renew Your ISSX Membership 14th European Meeting

12 13

ISSX Focus Groups Are Off and Running First Conference of SSX in Review

President’s Message

CALLING ALL NEW INVESTIGATORS!

Continued from previous page delivered his presentation on the Extended Clearance Concept at the end of September, and Dr. Dennis Smith will host a webinar on Physicochemistry and ADMET in January 2017. If you would like to submit topic recommendations for future ISSX webinars, please do so by completing this online form.

My best wishes to all for the coming holiday season, and as we move into the New Year, don’t forget to mark your 2017 calendar for the upcoming 14th European ISSX Meeting in Cologne, Germany, June 26–29 and the 21st North American ISSX Meeting in Providence, Rhode Island, USA, September 24–28.

Are you an ISSX Student Member or Regular Member within the first ten years of receiving your highest earned degree?

Would you like to be featured in ISSX Newsletter’s New Investigator Spotlight?

We’d love to hear from you!

Please contact ISSX at information@issx.org to indicate your interest in participating in this new opportunity.

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!

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UPCOMING ISSX MEETINGS 14th European ISSX Meeting

21st North American ISSX Meeting

6th Asia Pacific ISSX Meeting

Cologne, Germany

Providence, Rhode Island, USA

Hangzhou, China

June 26–29, 2017 Meeting Chair: Uwe Fuhr, Ph.D.

September 24–28, 2017 Meeting Chair: Jashvant Unadkat, Ph.D.

May 11–15, 2018 Meeting Co-Chairs: Su Zeng, Ph.D. and Jasminder Sahi, Ph.D.

22nd North American ISSX Meeting

12th International ISSX Meeting

23rd North American ISSX and 35th JSSX Meeting

Montreal, QC, Canada

Portland, Oregon, USA

Waikaloa, Hawaii, USA

July 15–19, 2018 Meeting Chair: Jack Uetrecht, M.D., Ph.D.

July 29–August 1, 2019

October 4–8, 2020 Meeting Co-Chairs: Allan Rettie, Ph.D. and Hiroshi Yamazaki, Ph.D.

Book Review ATTRITION IN THE PHARMACEUTICAL INDUSTRY: REASONS, IMPLICATIONS, AND PATHWAYS FORWARD Editors: A. Alex, C.J. Harris , D.A. Smith John Wiley and Sons Inc. 370pp., ISBN: 978-1-118-67967-8, 2016 The introductory chapter (pages 1–4) states the disappointing fact that during the last three decades or so, the rate of production of new drugs available for general usage has remained steady despite substantial increases in basic knowledge, technology and research, and development budgets. Taking these “failures” into consideration estimates the cost of bringing a new drug to the market lies at several billions of dollars, with the highest quote being $13 billion (pages 6/7).

Biological reasons for drug attrition can be divided (effectively) into toxicity or lack of efficacy, the latter usually owing to “poor pharmacokinetics or medically insignificant targets” (Chapter 10). Computer-assisted drug design and the use of other in silico approaches may reduce inappropriate choices of drug candidate molecules, but as highlighted, “Usually, in silico models are good at predicting new compounds that are similar and bad at predicting compounds that are very different from the training set compounds” (Chapter 10).

Seemingly of limited use for novel approaches.

Many case studies of potential drug compounds are presented to exemplify the points being made within the text, each chapter being followed by pertinent references that allow the reader to pursue further the topic raised.

A four-page index allows easy access to particular subjects. A well-constructed book containing a wealth of knowledge, much presented in table format, highly recommended.

Reviewed by

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

Book Ordering Information: John Wiley and Sons Corporate Headquarters 111 River Street Hoboken, NJ 07030-5774 United States of America Telephone: 201.748.6000 Fax: 201.748.6088 Email: info@wiley.com

The Atrium Southern Gate, Chichester West Sussex PO19 8SQ England Telephone: 44.1243.779777 Fax: 44.1243.775878 Email: customer@wiley.com

Issue 4, 2016

The content of this book “takes a comprehensive and holistic approach to problems and potential solutions to drug compound attrition.” Twenty four contributors have constructed 12 chapters entitled, “Attrition in drug discovery and development,” “Compound attrition at the preclinical phase,” “Attrition in Phase I,” “Compound attrition in Phase II/III,” “Postmarketing attrition,” “Influences of the regulatory environment on attrition,” “Experimental screening strategies to reduce attrition risk,” “Medicinal chemistry strategies to prevent compound attrition,” “Influence of phenotypic and target-based screening strategies on compound attrition and project choice,” “In silico approaches to address compound attrition,” “Current and future strategies for

improving drug discovery efficiency,” and “Impact of investment strategies, organizational structure and corporate environment on attrition, and future investment strategies to reduce attrition.”

/ISSX Newsletter / 3

ISSX Welcomes New Members Adebusuyi Ademisoye, Obafemi Awolowo University, Nigeria David Boyer, Achillion Pharmaceuticals, United States Erica Bradshaw-Pierce, Takeda Pharmaceuticals, United States

Josée Michaud, Altasciences Clinical Research, Canada Jamie Moscovitz, Pfizer, United States Rangaraj Narayanan, Celgene Corporation, United States David Neul, Dart Neuroscience, Inc., United States

Chris Brummel, Concert Pharmaceuticals, Inc., United States

Hoa Nguyen, Boehringer Ingelheim, United States

Peadar Cremin, Cytokinetics, United States

Grace Poon, Tesaro, Inc., United States

Tom De Vocht, KU Leuven, Belgium

Ellen Rohde, Cerulean Pharma, United States

Joi Dunbar, Biogen, United States

Yusuke Tanigawara, Keio University, Japan

Selvi Durmus Erim, Turkey

Charles Thompson, Merck, United States

Rajgopal Govindarajan, The Ohio State University, United States

Udomsak Udomnilobol, Chulalongkorn University, Thailand

Hiroshi Hasegawa, Shionogi Co., Ltd., Japan

Jin Wu, Merck, United States

Haiqing Hu, Celgene Corporation, United States

Zhaoming Xiong, Boehringer Ingelheim, United States

Lijuan Jiang, Enanta Pharmaceuticals, Inc., United States

Liu Yang, China

Alastair MacLeod, University of Dundee, United Kingdom Sravanthi Mannem, Sri Venkateswara Veterinary University, India

Muralidhar Yegireddy, Sri Venkateswara Veterinary University, India Helen Yu, Gilead Sciences, United States Mingshe Zhu, Bristol-Meyers Squibb, United States

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HAVE YOU ATTENDED AN ISSX WEBINAR? Supplement your learning by attending ISSX's online educational webinars, featuring world-renowned speakers and cutting-edge science. This benefit is offered exclusively to ISSX members. Join us on January 18, 2017 for Physicochemistry and ADMET presented by Dennis Smith, Ph.D. Register today at issx.org/webinar.

Past webinars and speakers include: • The Use of BDDCS to Predict Drug Disposition in Drug Development of NMEs

by Leslie Z. Benet, Ph.D. Recording available at issx.org/webinar/pastwebinars.

• Biosynthesis of Drug Metabolites for Use in DMPK Experiments and Late-Stage Lead Diversification by R. Scott Obach, Ph.D. • Use of “Extended Clearance Concept” and PBPK Modeling to Interpret Clinical Outcomes from In Vitro Metabolism and Transport Data; Focusing on the Transporters in the Liver by Yuichi Sugiyama, Ph.D.

New Investigator Spotlight Jessica Hartman, Ph.D., Postdoctoral Scholar Q: What are you currently researching/working on in your lab?

A: The focus of my postdoctoral research is studying the role of mitochondria-localized cytochrome P450 2E1 (CYP2E1) in driving neurodegeneration in the presence of CYP2E1-activated toxicants such as trichloroethylene and methanol.

These chemicals require CYP2E1 activity to exert their toxicity, and the mechanism of toxicity involves mitochondrial dysfunction. Therefore, my project centers on the hypothesis that CYP2E1 localized within mitochondria can generate reactive metabolites of these compounds in situ that damage mitochondrial proteins and DNA and lead to dysfunction.

To address this question, I am creating transgenic models expressing human CYP2E1: a cell culture model based on a rat PC-12 background (neuronal cells that can be differentiated to dopaminergic and other fates), and Caenorhabditis elegans nematodes. Both model systems lack basal CYP2E1 activity and therefore do not have undesirable background activity. In each system, I will introduce wild-type CYP2E1 (which will localize both to mitochondria and endoplasmic reticulum), mitochondria-targeted CYP2E1, or endoplasmic reticulumtargeted CYP2E1. I will then see if mitochondrial localization sensitizes cells or animals to exposures to trichloroethylene and methanol. I will measure in vitro and in vivo mitochondrial dysfunction, as well as organismal toxicity including neurodegeneration.

Continued on next page

/ISSX Newsletter / 5

Service Award (NRSA) F32 postdoctoral fellowship from the National Institute of Environmental Health Sciences.

This will allow me to pursue my postdoctoral work in the lab of Dr. Joel Meyer in the Nicholas School of the Environment at Duke University. In my project, which I began in July, I am building on the biochemical foundation from my graduate work to study the role of mitochondria-localized CYP2E1 in neurons, and how its activity may be involved in trichloroethyleneand methanol induced neurodegeneration. It is so exciting to move into the field of toxicology and observe consequences of the biochemical activation of chemicals.

Issue 4, 2016

Q: What led you to become interested in this particular field?

A: My interest in mitochondrial toxicity and neurodegeneration began during my graduate studies.

My graduate work, which I shared with the ISSX community at multiple meetings through poster abstract presentations, identified novel examples of cooperativity in the kinetic mechanism of cytochrome P450 2E1 (CYP2E1) metabolism in the liver. During that time, I read about new studies of mitochondrial CYP2E1 localized in various extrahepatic tissues and became very interested in how this form could impact toxicity.

I defended my dissertation in April 2016 and graduated in May 2016. I was fortunate to be selected as a recipient of the Ruth Kirschstein National Research

New Investigator Spotlight Continued from previous page

Q: What do you value most about your ISSX membership?

A: ISSX meetings have always been so enjoyable to attend – I appreciate that the community is a blend of researchers from academia, industry, and government and I always receive excellent feedback on my work when I present at the meetings. I have also had the wonderful opportunity to participate in planning a young investigator session for the 2015 North American ISSX Meeting and found this to be a great experience both in planning and execution. Working hand-in-hand with senior members of ISSX allowed me to learn how meetings are organized and gave me the chance to meet many ISSX senior investigators and young investigators. This is a society that is placing increasing emphasis on encouraging and training young investigators and I think the wealth of expertise and support in the society is invaluable to that cause.

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Q: Who is your mentor/role model?

A: One of the most difficult decisions a young scientist makes is choosing the labs in which to do their graduate and postdoctoral. Through a combination of luck and careful deliberation, I have managed to end up with wonderful choices for both. My graduate advisor, Grover Miller, is an admirable scientist and excellent mentor who has always been willing to lend an ear and offer advice on my research, career, and life. Grover has taught me a great deal scientifically and ethically and will always be a mentor and friend to me. When I met my postdoctoral advisor, Joel Meyer, I knew instantly that I would enjoy working for him. One of the most

striking things about visiting and getting to know Joel is that every single person I talked to who knew him said the same thing: “Joel is really great.” (I hope one day to have that kind of reputation.) Although I have not been in the lab very long, I can already see that working with Joel has helped me to improve my work style, expand my knowledge, and start to establish myself as an independent researcher.

Q: What advice do you have for other new investigators?

A: My advice to new investigators in ISSX is to get involved! The greatest things I have been able to accomplish as a researcher have been through collaborations, and finding great collaborators requires first meeting and talking to other researchers. Societies like ISSX are a great place to get to know other people and getting involved in the organization and attending scientific meetings gives you a chance to really connect with others in your field. My other piece of advice is to keep yourself organized and keep track of short- and long-term goals; I find it is best to actually do this in a tangible way and not just in the abstract. Keeping daily lists of tasks and weekly/monthly goals is a great way to make sure you are moving forward. I also like to make and regularly update a flow chart/map of my project(s) as it evolves to try to keep my eye on the big picture. And finally, try to drive your experiments so that they tell a story, which requires more thinking on the front-end but leaves you with more or less complete publishable units without a lot of “extra” data that doesn’t fit.

MAKE PLANS TO ATTEND! Visit issx2017na.com for more information!

Header ISSX Workshop in Review The ISSX Workshop, Translating Preclinical Data to Human Clearance and Pharmacokinetics (PK), was held at the Sheraton Boston Hotel in Boston, MA, USA October 27–28. The workshop, co-chaired by Yingying Guo from Eli Lilly and Company and Jin Zhou from Boehringer Ingelheim, brought together more than 200 participants, exhibitors, and speakers.

The two-day workshop was devoted to analyzing the challenges of predicting human clearance and PK. It began with a short course to update attendees on the current status and challenges in predicting human PK and to assess the application of physiologically based pharmacokinetic (PBPK) modeling. Building on these concepts, the workshop proceeded to presentations and discussions on methodologies utilized to address key issues and proposed next steps in human PK/clearance predictions. These methodologies included 1) examining state-of-the-art in vitro technologies, combined with modeling approaches to address clearance prediction for low clearance and highly bound compounds; 2) addressing challenging issues in PK/clearance prediction for non-CYP enzymes, including UDPglucuronosyltransferases (UGTs), aldehyde oxidase, and carboxylesterases; 3) discussing approaches to predict

WORKSHOP ORGANIZING COMMITTEE COMMITTEE CO-CHAIRS Yingying Guo, Eli Lilly and Company and Jin Zhou, Boehringer Ingelheim COMMITTEE MEMBERS Aleksandra Galetin, University of Manchester Stephen D. Hall, Eli Lilly and Company Donald Tweedie, Merck & Company

human hepatobiliary transporter-mediated clearance; and 4) examining experimental and modeling/simulation approaches for PK prediction in special populations.

The workshop extended discussions on two practical strategies utilized in the pharmaceutical industry for human PK/clearance prediction, recognizing that there may not be universal solutions for every problem. First, the interplay of enzymes and transporters is at the core of current approaches for human PK/clearance

Issue 4, 2016 ISSX Workshop participants attend a scientific session.

Continued on next page

/ISSX Newsletter / 7

An ISSX Workshop attendee views the poster abstracts on display.

ISSX Workshop Continued from previous page

hepatocyte relay method, and liver chips, may be useful in characterizing low metabolic clearance compounds.

There are clear gaps in prediction of human PK clearance mediated by non-CYP enzymes and by transporters. Proteomic technology, humanized animal models, and sandwich-cultured hepatocytes, may have value in bridging some of the gaps. PBPK has been increasingly used in drug development and regulatory submissions. Confidence in using PBPK to predict CYP-related drug-drug interactions has been increasingly demonstrated. The approach also shows promise for predicting PK of special populations. However, there remain uncertainties for many diseases and age-related physiological parameters and the science of using PBPK in special populations continues to evolve.

ISSX Workshop attendees discuss a poster abstract. prediction. Consequently, the traditional well-stirred model concept is being replaced by the extended clearance model. The shift has created new challenges in the characterization of compound clearance as well as those tools used for characterization, which are subsequently impacting drug discovery and development.

Second, in vitro and in vivo experimental systems, in conjunction with modeling approaches, are finding utility, particularly with some challenging scenarios of human PK/clearance prediction. For instance, in vitro tools such as long-lived hepatocyte culture systems, the

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ISSX THANKS OUR EXHIBITORS Absorption Systems Ascendance Bio BioreclamationIVT Corning Hera BioLabs, Inc. Horizon Discovery MicroConstants Optivia Biotechnology Phoenixbio Co., Ltd.

QPS, LLC Qualyst Transporter Solutions, LLC Sekisui XenoTech Simulations Plus, Inc. SOLVO Biotechnology Triangle Research Labs / Lonza WuXi-XBL

This workshop aimed to inspire future discussion and catalyze collaborative efforts to address some unsolved challenging issues. Thirty-three abstracts were accepted and these posters were available for viewing.

All accepted abstracts and speaker presentations are available to members through the members-only section of the ISSX website.

ISSX appreciates the commitment and efforts of the Workshop Organizing Committee, ISSX staff, speakers, and attendees who made this endeavor a remarkable success.

ISSX THANKS OUR WORKSHOP SUPPORTERS AbbVie Bristol-Meyers Squibb Genentech Lilly Pfizer

Renew Your ISSX Membership for 2017 ISSX’s membership term runs on an annual basis beginning January 1 and ending December 31.

Membership dues for the 2017 membership year should be received before December 31, 2016.

Renewing your ISSX membership is easy! We strongly encourage you to utilize our immediate, secure online renewal system. To renew your membership online: 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. Once you verify 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.

ISSX members have access to a variety of exclusive benefits including: •R educed registration fees for all ISSX meetings and workshops; •O nline learning opportunities including free registration for ISSX's educational webinars, featuring world-renowned speakers and cuttingedge science; •A subscription to the ISSX Newsletter that highlights Society news, member spotlights, late-breaking scientific news, and much more; •S pecial journal subscription discounts to multiple scientific journals; •T he opportunity to submit and present scientific abstracts at ISSX meetings; •E ligibility to apply for and receive travel grants to attend ISSX meetings; •T he chance to hold office, serve on a committee, and vote in ISSX elections; • And more!

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 sent to you via email. Please print the invoice and submit it with your check payment to:

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.

/ISSX Newsletter / 9

issx.org/renew

Issue 4, 2016

ISSX 8652 Solution Center Chicago, IL 60677-8006

Your membership indicates your support of our mission to advance research and education on the interplay of living systems with medicines and chemicals for the benefit of society worldwide and helps sustain our program of operations. Visit issx.org/renew today!

Gร RZENICH | COLOGNE, GERMANY | 26 - 29 JUNE 2017

Register before 16 February 2017 and save! issxeuro2017.org

REGISTRATION Early discounted rates (in USD including 19% German VAT) are listed below. Register for two short courses and save 25%! Rates increase 16 February. Save and register today at issxeuro2017.org.

ONE TWO

SHORT COURSE SHORT COURSES

MEETING REGISTRATION

BANQUET TICKET

ISSX MEMBER

$215 $322 $792 $125

NONMEMBER

$280 $417 $956 $125

STUDENT MEMBER

$119 $179 $328 $75

STUDENT NON-MEMBER $149 $227

$357 $75

TRAVEL & LODGING Traveling to Cologne is easy. Details concerning travel, airline discounts, lodging, passport and visa requirements, and much more are provided on the meeting website.

We strongly encourage participants to reserve lodging early. Secure your accommodations soon and receive a KรถlnCard voucher valid for free travel on public transportation in Cologne.

MEETING ORGANIZING COMMITTEE

Dear friends and colleagues, On behalf of the Meeting Organizing

oldest and most attractive vaulted wine

Committee, it is my great pleasure to

cellars in the country.

CHAIR: Uwe Fuhr, University Hospital Cologne

invite you to the 14th European Meeting of

Thomas Baillie, University of Washington

the International Society for the Study of

A 2,000-year-old city spanning the Rhine

Xenobiotics (ISSX), 26 – 29 June 2017 in

River in western Germany, Cologne is the

Cologne, Germany – the premier European

region’s cultural hub. It is home to more

meeting in 2017 exploring the interplay of

than thirty museums and hundreds of

living systems with medicines and chemicals.

galleries. Great dining, shopping, history,

This meeting will provide a wonderful

and more await you. Bring your family

opportunity to exchange ideas and expertise,

and extend your stay to make this your

to develop a common vision, and to create

unique summer holiday.

Dirk Gründemann, University Hospital Cologne Dieter Lang, Bayer HealthCare AG Mario Manshouwer, Janssen Research & Development Edmund Maser, Christian-Albrechts-Universität zu Kiel Scott Obach, Pfizer, Inc.

and nurture collaborations.

Stefan Oswald, Universitätsmedizin Greifswald

Please take this opportunity to expand and The 14th European ISSX Meeting features

share your knowledge on the interaction of

three excellent short courses, thirteen

foreign chemicals with living systems, renew

scientific symposia encompassing a broad

or develop friendships with colleagues from

spectrum of topics, state-of-the-art lectures,

around the world, and enjoy all that the

and scientific lectures by the recipients of

wonderful city of Cologne offers.

Jens Riedel, Sanofi-Aventis Deutschland GmbH Gerhard Schänzle, Boehringer Ingelheim Pharma GmbH & Co. KG

the European Scientific Achievement Award and the European New Investigator Award in

Matthias Schwab, Dr. Margarete Fischer-Bosch-Institut für Klinische Pharmakologie

Sincerely,

Honor of Karl J. Netter. Poster sessions, a trade exhibition, and industry-sponsored symposia

Prof. Dr. Uwe Fuhr

complement the meeting. On the social side,

Meeting Organizing Committee Chair

Fritz Sörgel, Institute for Biomedical and Pharmaceutical Research

we are planning a festive dinner at one of the

Center of Pharmacology, University Hospital Cologne

Geoff Tucker, University of Sheffield

PROGRAM

Tentative, as of December 2016

Short Courses

Symposia

Primary Human Hepatocytes: Basic Aspects

Integrated Pharmacogenomics

Advanced Culturing of Human Hepatocytes Quantifying the in vivo Acticity of Human Drug Metabolizing Enzymes and Transporters

New Investigators’ Forum: Skills Needed for DMPK Scientists

Indication-Specific Challenges for Drug Discovery and Development

P(esticide)MPK and Human Health Risk Assessment

Approaches to Quantify the in vitro Function of ABC Efflux Transporters

The Impact of Disease State on Xenobiotic Metabolism

Keynote

Risk Assessment and Regulatory Expectations of Nucleotides in Drug Development

Ribosomes as Targets for New Antibacterials

Recent Technology Advancements Relevant for Drug Discovery and Development

State-of-the-Art Lectures

Strategies to Improve Drug Safety in Clinical Development

Undruggable Targets CYP2D6: A Paradigm for Understanding Genetic Variability in DMPK The Promise of and Challenge of Cancer Epigenetics

Non-Standard Enzymes in Drug Metabolism

PBPK Beyond PK of Small Molecule Drugs

Acquisition and Implementation of DDI Information Applicable for Individual Treatment Understanding and Targeting the Human Microbiome

Register before 16 February 2017 and save! issxeuro2017.org

PRESENT YOUR RESEARCH AT THE MEETING

AWARDS

Presenting a poster brings focus to your important research. Presenters will showcase their research during one of three poster viewing sessions and networking sessions provide attendees time with posters and presenting authors. Students and recent postdocs may submit abstracts in the Poster Awards Competition and win prizes! Submit your abstract to

Nominate deserving colleagues for our prestigious scientific awards to be presented at the meeting in a special session. Nominations are due 31 March 2017. Visit the meeting website to learn how to submit a nomination.

issxeuro2017.org by 26 February 2017.

ISSX Focus Groups Are Off and Running We are thrilled to announce that the formation of the initial ISSX Focus Groups is complete. Chairs and co-chairs for each of our three Focus Groups have been appointed and initial activities are underway. The Focus Groups and their leaders are: Biotransformation Mechanisms & Pathways Chair: Amit Kalgutkar (Pfizer) Co-Chair: Barry Jones (AstraZeneca)

Bioanalysis in ADME Science Chair: Mingshe Zhu (Bristol-Myers Squibb) Co-Chair: Kevin Bateman (Merck) Participation in ISSX Focus Groups is included with the standard annual dues assessment and members may choose to join one or more groups. While the long-term objectives of each group may evolve, the initial purposes include:

•S timulating communication between ISSX members from around the world;

•E nabling members to provide specific input into meeting program planning and on-line education initiatives; •D eveloping position papers on emerging issues relevant to the fate of xenobiotics;

Modelling & Simulations Chair: Hartmut Derendorf (University of Florida) Co-Chair: Yusuke Tanigawara (Keio University, Tokyo)

•E ncouraging the involvement of members in ISSX affairs;

• Generating new membership in the Society;

•E nhancing interaction and collaboration with other societies interested in the interplay of living systems with medicines and chemicals.

Routine communication will be essential and one way to facilitate this is through group specific forums where members may post questions, comments, materials, and links to interesting and relevant online resources.

Content about each group’s activities will appear in the ISSX Newsletter and, in the future, group members can meet in-person at ISSX meetings.

Associating and actively participating in a focus group can significantly enhance the exchange of the most current scientific research information and open doors to endless opportunities for collaboration and career advancement. We hope that active participation provides personal growth and professional development to ISSX members.

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CELEBRATING 35 YEARS OF ISSX 2016 marks the 35th anniversary of ISSX. Over the past 35 years, ISSX has increased its membership, held highly-regarded scientific meetings, and has grown into the premier scientific organization for researchers interested in the metabolism and disposition of xenobiotics.

ISSX would not be the association that it is today without the leadership and dedication of ISSX Council and Society members. ISSX wishes to thank each and every member for their valued time, effort, and participation—without which ISSX would not have reached this milestone.

First Conference of the Indian Society for the Study of Xenobiotics in Review The First Conference of the Indian Society for the Study of Xenobiotics (SSX) was held August 31–September 3 in Bangalore, India. SSX, an affiliate society of ISSX, was created to share knowledge and training information related to DMPK/ADMET sciences in India and the surrounding region. The focus of SSX, while currently centered around the organization of the annual conference in India, will expand to include local discussion groups and networking opportunities within the next two years.

The First Conference of SSX, chaired by Murali Subramanian of Syngene/BBRC in India, began on August 31 with a pre-conference workshop hosted

by Simcyp at the M. S. Ramaiah University of Applied Sciences. Forty-five scientists from India and neighboring countries attended lectures and participated in hands-on training at this vigorous workshop led

by Masoud Jamei and Nikunj Kumar Patel. The main conference was held at the prestigious JN Tata auditorium, part of the premier Indian Institute of Science. Due to an unexpected labor strike on September 2, the conference schedule was reduced to September 1 and September 3 only. Despite the schedule change, the full scientific program was accommodated and attendance was not affected. A

total of 212 participants from 12 countries attended the main conference, with 75% representing Industry and 25% representing Academia. There were 44 posters on display from more than 30 organizations, and the conference was supported by 23 sponsors. The program was divided into six sessions: Mechanisms of DrugInduced Toxicity chaired by Tom Baillie, Drug Disposition and Drug Interaction chaired by Peter Fan, PK/PD Modeling chaired by Eric Chan, Transporters chaired jointly by Jash Unadkat and Berend Oosterhuis, Personalized Medicine chaired by Magnus Ingelman Sundberg, and DMPK in Drug Discovery chaired by Larry Wienkers. On the evening of September 1, SSX hosted a grand dinner reception to celebrate the society’s inaugural conference. Overall, the First Conference of SSX exposed the audience to fundamental and cutting-edge concepts in all areas of DMPK/ADMET and fostered discussion and networking after every lecture.

The First Conference of SSX was a resounding success with greater than expected participation, high-quality lectures by leading scientists, stimulating discussions, numerous posters that allowed scientists in the region to showcase their work to an international audience, Continued on next page

Issue 4, 2016

An SSX Meeting speaker delivers a scientific talk.

/ISSX Newsletter / 13

An SSX Meeting attendee views the poster abstracts.

First Conference of SSX in Review Continued from previous page

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SSX Meeting attendees. and strong support from vendors resulting in unanimous positive feedback. SSX invites you to attend its Second Annual Conference which will be held October 25–28, 2017 in the JN Tata Auditorium of the Indian Institute of Science in Bangalore, India. SSX is currently looking for volunteers to serve on various conference organizing committees, as well as speakers for the upcoming conference. If you are interested, please contact Murali Subramanian via email at msubramanian@issx.org.

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

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.

Deadline for the submission of material to the ISSX Office: ISSUE

MATERIALS DEADLINE*

RELEASE DATE

Issue 1, 2017

January 20, 2017

February 2017

Issue 2, 2017

April 14, 2017

May 2017

Issue 3, 2017

July 14, 2017

August 2017

Issue 4, 2017

October 20, 2017

November 2017

*

Subject to change

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

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.

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