Sunday, September 11, 2022

Program subject to change.

9:00 am - 12:00 pm | Concurrent Short Courses 1 and 2

Short Course 1: Fundamentals of Bioanalysis for Proteins, Cell and Gene Therapy, Organized by the Bioanalysis in ADME Science Focus Group
Chairs: Lucinda Hittle, Merck, Rahway, New Jersey, USA and Matthew Albertolle, Takeda Pharmaceuticals, San Diego, California, USA

Background: The explosive growth of modalities beyond small molecules has led to a commensurate expansion in the breadth of bioanalytical techniques leveraged to answer key questions around drug metabolism, pharmacokinetics and translational pharmacokinetics/ pharmacodynamics. This course will provide a survey of key techniques to familiarize attendees with technical features of these assays as well as their application to solve critical problems and enable rapid, effective decision making in drug discovery and development. Emphasis will also be placed on method design, qualification and validation where appropriate.

In this course the participants will learn: An overview of four unique dimensions of bioanalysis for proteins, cell and gene therapy, including: 1) Ligand Binding Assays, 2) Liquid Chromatography/Mass Spectrometry for Large Molecules, 3) PCR including digital droplet techniques, and 4) Immunogenicity. Each section will be taught by an experienced industrial scientist in this discipline, and include relevant case studies and applications.

Fundamentals of PCR Including Digital Droplet Techniques
Matthew Albertolle, Takeda Pharmaceuticals, San Diego, California, USA

Fundamentals and Applications of LC/MS and CE/MS for Large Molecules Bioanalysis
Mei Han, Amgen, Inc., South San Francisco, CA, USA

Impact of Novel Ligand Binding Assay Technologies on Bioanalysis
Sally Fischer, Genentech, South San Francisco, California, USA

Fundamentals of Immunogenicity
Marina Li, Merck, Whitehouse Station, New Jersey, USA

Short Course 2: Addressing ADME Models and Challenges of New Candidates to Better Translate in vitro to in vivo: (a) investigating low clearance drugs, (b) defining the role of the gut microbiome and (c) normalizing the use of microfluidic systems for biotransformation and toxicity
Chairs: Rheem Totah, University of Washington, Seattle, Washington, USA, and Deepak Dalvie, Crinetics Pharmaceuticals, San Diego, California, USA

Background: This short course will focus on challenges and advances that biotransformation scientists face when translating in vitro to in vivo.  We will discuss the challenges associated with low clearance drugs.  Low clearance drugs are desirable due to limited metabolism, decreased potential for DDIs, longer half-life and the promise of a lower dose. But despite these attributes, several in vitro tools can lead to overestimation of dose, clearance and half-life below a certain intrinsic clearance value. The latest advances in in vitro tools to tackle these challenges will be discussed to improve IVIVC.  Another consideration for better in vivo prediction, is the involvement of the gut microbiome in the metabolism and clearance of certain drugs. Understanding the role of the gut microbiome can be crucial to improving in vivo prediction. In vitro approaches to tackle low clearance drugs and the gut microbiome will be introduced as well as strategies to translate to in vivo for better prediction will be presented.  The use of microfluidic systems to investigate biotransformation and toxicity at early stages of development can be advantageous and reduce the need for preclinical animal testing. The latest advantages and tools available for biotransformation scientists will be discussed.

In this short course the participants will learn: 1) the in vitro ADME challenges of low clearance drugs, 2) the latest advances in in vitro tools to improve IVIVC using real drug examples, 3) the involvement of the gut microbiome and its role in biotransformation and effect on drug clearance, 4) the latest in vitro approaches to investigate involvement of the gut microbiome in biotransformation and 5) recent developments to apply microfluidic systems to study biotransformation and toxicology.

Low Clearance and Unique Metabolic Pathways: A New Challenge in the Biotransformation Studies of Drug Candidates
Deepak Dalvie, Crinetics Pharmaceuticals, San Diego, California, USA

In vitro Tool Kit to Measure Metabolic Stability and Metabolic Profile of Low Clearance Drugs
Li Di, Pfizer, Groton, Connecticut, USA

The Role of the Gut Microbiome in Metabolism of Drugs
Aaron Wright, Baylor University, Waco, Texas, USA

Application of Microfluidic Systems in Mechanistic Nephrotoxicity Studies of Drugs & Xenobiotics
Edward Kelly, University of Washington, Seattle, Washington, USA

12:00 pm - 1:00 pm | Short Course Attendee Lunch

1:00 pm - 4:00 pm | Concurrent Short Courses 3 and 4

Short Course 3: State of Science of PBPK 2022: Beyond P450s
Chairs: Yuan Chen, Genentech, South San Francisco, California, USA, and Oliver Hatley, Certara, Sheffield, United Kingdom

Background: Physiologically-based pharmacokinetic and pharmacodynamic (PBPK-PD) modeling and simulations are routinely used in today’s drug development and regulatory assessments to support dosing decisions. The majority of the “high impact” uses are to manage clinical drug-drug interactions. In recent years, the science of PBPK has evolved significantly in areas beyond drug metabolism via P450s. After a successful event for 2021 ISSX annual meeting, the M&S Focus Group is pleased to organize and announce the PBPK Short Course for 2022 ISSX/MDO meeting in Seattle.

In this short course, participants will learn: the state of the science of PBPK in the areas of predicting oral drug absorption, development of physiology models for virtual specific populations, prediction of transporter mediated DDIs, and advancement on modeling non-CYP metabolism and related DDIs from regulatory perspectives. We designed the short course to allow ample interactions between participants and speakers.

Absorption Predictions: Current Capabilities and Knowing the Gaps
Viera Lukacova, Simulations Plus, Inc., Lancaster, California, USA

Understanding Physiology and Systems Parameters in Special Population Models
Oliver Hatley, Certara, Sheffield, United Kingdom

Current Capabilities in Modeling Transporter-mediated DDIs
Bridget Morse, Eli Lilly, Indianapolis, Indiana, USA

Overview and Advancements in Modeling Non-CYP Metabolism and Associated DDIs
Xinyuan Zhang, Daiichi Sankyo, Inc., Basking Ridge, New Jersey, USA

Short Course 4: Transporter Phenotyping: from Qualitative Characterization to Quantitative Prediction
Chairs: Xiaoyan Chu, Department of ADME and Discovery Toxicology, Merck & Co. Inc. Kenilworth, NJ, USA , and Xinning Yang, Office of Clinical Pharmacology, US Food and Drug Administration, Silver Spring, Maryland, USA

Background: Drug transporters, acting alone or in concert with drug metabolizing enzymes, can play an important role in modulating drug absorption, distribution, metabolism, and excretion (ADME), thus affecting the pharmacokinetics (PK), and/or pharmacodynamics (PD) of drugs.  Interaction of drug molecules with transporters may cause clinically significant drug-drug interactions (DDIs) and toxicity. Therefore, characterization of transporter phenotyping of a drug, understanding, and predicting its clinical relevance is important for drug discovery and development.  

This short course aims to introduce theoretical concepts and elucidate in vitro, in vivo, and mechanistic modeling approaches to study transporter phenotyping with the goals to provide quantitative prediction of the contribution of transporters on PK, DDIs, and tissue exposure of drugs in humans.

In this short course, participants will learn: 1) the concepts and approaches to study the role of transporters in drug disposition in drug discovery and development; 2) how to apply various in vitro and preclinical models to characterize transporter phenotyping and extrapolate to in vivo in human, and limitations of these models; 3) utility of pharmacogenetic analysis in transporter phenotyping and usefulness of biomarkers to assess clinical implications of transporters-mediated DDIs. 4) mechanistic static and PBPK modeling to predict transporter-mediated PK and DDIs.

Application of Extended Clearance Concept and Extended Clearance Classification System (ECCS) to Predict Clearance Mechanism in Drug Discovery
Manthena Varma, Pharmacokinetics, Dynamics and Metabolism, Medicine Design, Worldwide R&D, Pfizer Inc, Groton, Connecticut, USA

In vitro Assays to Study Transporter Phenotyping: Considerations on Study Design and Mechanistic Modeling
Sibylle Neuhoff, Simcyp Division, Certara UK Limited, Sheffield, United Kingdom

Relative Expression and Activity Factors-based Approaches to Predict the Contribution of Transporters to Drug Disposition
Per Artursson, Department of Pharmacy, Uppsala University, Uppsala, Sweden

Endogenous Biomarker-informed Approach to Evaluate Clinical Implications of Transporter-mediated PK and DDIs
Aleksandra Galetin, Centre for Applied Pharmacokinetic Research, School of Health Sciences, The University of Manchester, Manchester, United Kingdom

5:00 pm - 6:00 pm | Focus Groups Meet-Up

Networking Session

Additional details to be announced.

6:00 pm - 6:15 pm | Opening Welcome

Welcome Remarks

ISSX/MDO 2022 Meeting Co-Chairs, Michael Zientek, Takeda Pharmaceuticals, San Diego, California, USA, and Xiaobo Zhong, Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut, USA

Scott Obach, ISSX President, Pfizer, Groton, Connecticut, USA

Magnus Ingelman-Sundberg, MDO, Karolinska Institute, Stockholm, Sweden and Xinxin Ding, MDO, R. Ken Coit College of Pharmacy, University of Arizona, Tucson, Arizona, USA

6:15 pm - 7:45 pm | Opening Keynote Event

Perspectives on Long-held Clearance Concepts
Moderated by Scott Obach, Pfizer, Groton, Connecticut

Featuring lectures from Leslie Z. Benet, UCSF School of Pharmacy, San Francisco, California, USA and K. Sandy Pang, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada and a robust panel discussion including distinguished panelists William J. Jusko, School of Pharmaceutical Sciences, University at Buffalo, Buffalo, New York, USA, Ken Korzekwa, Temple University, Philadelphia, Pennsylvania, USA, and Jasleen Sodhi, South San Francisco, California, USA

The Model Independent Clearance/Intrinsic Clearance Equation
Leslie Z. Benet, UCSF School of Pharmacy, San Francisco, California, USA

Demystifying Model-independent and Model-dependent Clearance Concepts and Equations
K. Sandy Pang, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada

7:45 pm - 9:45 pm | Opening Welcome Reception

Networking Event
Sponsored by Sekisui XenoTech


All attendees are invited to meet with fellow attendees, speakers, and our sponsoring and exhibiting partners who will be on-hand to share information about their latest products and services.