Sunday, September 10, 2023
Program subject to change.
9:00 am - 12:00 pm | Concurrent Short Courses 1 and 2
Short Course 1: Best Practices for In Vitro enzyme (CYP, UGTs) and Clinical Study Design (encompasses PBPK) to Support DDI Studies & Product Labeling | Marina Ballroom I-II
Chairs: Li Di, Pfizer, Groton, Connecticut, USA and Fatemeh Akhlaghi, Pfizer, San Diego, California, USA
Background: This short course will cover current best practices and regulatory guidance around in vitro studies assessing inhibition and induction of CYPs and UGTs, the use of the in vitro data to project DDIs using static and PBPK modeling, as well as the use of the data to design clinical DDI studies and inform product labels. The lectures will discuss fundamental mechanisms of enzyme inhibition and induction with examples of classic DDIs from the literature for CYPs and UGTs. Successes around prediction accuracy using various models will be highlighted.
Assessing Victim Drug-drug Interaction – Reaction Phenotyping of CYP and non-CYP
Li Di, Pfizer, Groton, Connecticut, USA
CYP and UGT Inhibition to Assess Perpetrator Drug-drug Interaction Potential
Mike Zientek, Takeda, San Diego, California, USA
Enzyme Induction Fundamentals, Assays, Data Interpretation and in vivo Translation
Diane Ramsden, AstraZeneca, Waltham, Massachusetts, USA
Clinical DDI Trial Design and Impact on Product Labels
Fatemeh Akhlaghi, Pfizer, San Diego, California, USA
Short Course 2: State-of-the-art on the ADME of Protein Therapeutics | Marina Ballroom III-IV
Chairs: Dhaval Shah, University at Buffalo, Buffalo, New York, USA and Brooke Rock, Amgen, Inc., Bend, Oregon, USA
Background: This short course is designed to provide the audience with state-of-the-art perspectives on the pharmacokinetics (PK) of protein therapeutics. The first lecture will focus on the mechanisms of clearance, disposition/ biodistribution, and absorption (subcutaneous, oral!) of protein therapeutics. A vision for the development of quantitative structure-pharmacokinetic relationships (QSPKR) for protein therapeutics will be presented using empirical relationships and PBPK models developed for protein therapeutics. The second talk will focus on various in vitro assays, ex-vivo assays, and in vivo screening assays developed to rapidly assess or predict the PK property of protein therapeutics. The third talk will focus on the utilization of novel transgenic animals and PBPK models for the prediction of clinical PK of protein therapeutics. The last talk will focus on how to exploit the knowledge about the determinants for the PK of protein therapeutics to design better/optimal molecules with desired PK and pharmacology.
Basic Tenets for the ADME of Protein Therapeutics
Dhaval Shah, University at Buffalo, Buffalo, New York, USA
In vitro and in vivo Systems for Predicting the ADME of Protein Therapeutics: Are We There Yet?”.
Brooke Rock, Amgen, Inc., South San Francisco, California, USA
Beyond Non-human Primates: Transgenics and PBPK Models for Predicting the Human PK of Protein Therapeutics
Alison Betts, Takeda, Boston, Massachusetts, USA
Engineering Proteins to Achieve Desired ADME Characteristics
Javier Chapparo-Riggers, Pfizer, San Diego, California, USA
12:00 pm - 1:00 pm | Short Course Attendee Lunch | Commonwealth Ballroom
1:00 pm - 4:00 pm | Concurrent Short Courses 3 and 4
Short Course 3: Strategies That Enable Successful FIH and Beyond | Marina Ballroom I-II
Chairs: Christine Fandozzi, J&J, Springhouse, Pennsylvania, USA and Rosa Sanchez, Merck, West Point, Pennsylvania, USA
Background: This short course is aimed at scientists desiring to gain experience in successful IND submissions that enable first-in-human (FIH) studies with clear line of sight to successful approvals. The course is broken into three parts with three experienced lecturers across industry and FDA. The first section will cover translational aspects, modeling approaches, and FIH exposure/dose predictions in the context of the desired therapeutic benefit. The next section will focus on the work needed in the preclinical toxicology package (e.g. expected mechanism-based toxicity, off-target toxicity, species selection, target exposure/dose justifications and metabolites). The last section will focus on the understanding the absorption, distribution, metabolism, and excretion (ADME) of the investigational drug with a particular emphasis on drug-drug interactions and inclusion/exclusion criteria in the initial FIH studies and the long range view towards drug approval.
A Successful Preclinical Toxicology Package
Shaji Theodore, US Food and Drug Administration, Silver Spring, Maryland, USA
ADME considerations from FIH to Drug Approval
Rosa Sanchez, Merck, West Point, Pennsylvania, USA
Pharmacology and Translational Aspects
Mirjam Trame, Certara, Boston, Massachusetts, USA
Short Course 4: Transporter Substrate/Inhibition/Induction, DDI | Marina Ballroom III-IV
Chairs: Yurong Lai, Gilead and Jason Sprowl, University at Buffalo, Buffalo, New York, USA
Background: This short course will focus on challenges and advances of transporter mediated drug disposition and translation from preclinical to human. Drug transporters play an important role in drug disposition, and are often associated with organ toxicity. The short course will discuss the transcriptional and post-transcriptional regulation of transporters and the outcomes of the regulation. The ICH M12 step 1 draft guideline is published and currently under public consultation. The short course will also discuss the similarity and difference between ICH M12 and the current regulatory guidance, and its application. The conventional allometric method to predict of human dose and pharmacokinetics remains challenging for transporter substrate. The short course will introduce the application of PBPK modeling approaches including model development and validation in preclinical species as an optimal tool to translate in vitro transport kinetics to in vivo situation. Assessing transporter drug-drug interactions can be crucial in drug development, and many endogenous metabolites are identified as useful markers for transporter DDIs. The latest advantages of using transporter DDI biomarkers will be discussed.
Clinical Studies on Pharmacogenomics and DDIs Involving Drug Transporters
Xinning Yang, US Food and Drug Administration, Silver Spring, Maryland, USA
Considerations of Endogenous Biomarkers to Assess Transporter DDIs in Early Drug Development: An IQ Update and Beyond
Bridget Morse, Eli Lilly and Co., Indianapolis, Indiana, USA
Drug Induced Organ Toxicity: Transporter Roles and Derisking Approaches
Jason Sprowl, University at Buffalo, Buffalo, New York, USA
Approaches to Predict Human PK Profiles for Compounds Undergoing Transporter Mediated Clearance in Early Drug Development: From Dedrick Plot to PBPK Modeling
Xiaomin Liang, Gilead Sciences, Inc. Foster City, California, USA
4:00 pm - 5:45 pm | Focus Groups Meetings
4:00 - 4:45 pm | Concurrent Focus Group Session 1
Biotransformations, Mechanisms, and Pathways Focus Group
Chair: Valerie Kramlinger, Vanderbilt University and Co-Chair: Aaron Teitelbaum, Boehringer Ingelheim
Agenda:
1. Welcome from Focus Group Chairs and Overview of the Focus Group Purpose and Goals
2. Networking/job session: Skillsets you need in biotransformation
3. Rapid fire presentations for trainees
4. Thanks and Adjourn
Transporters Focus Group
Chair: Xinning Yang, FDA and Co-Chair: Bhagwat Prasad, Washington State University
Agenda
1. Welcome from Focus Group Chairs and Overview of the Focus Group Purpose and Goals
2. Overview of events/webinars/publications/updates since last Focus Group meeting in September 2022
3. Overview of upcoming events/webinars/publications
4. Thanks and Adjourn
5:00 - 5:45 pm | Concurrent Focus Group Session 2
Bioanalysis in ADME Science Focus Group
Chair: Matthew Albertolle, Takeda Development Center Americas (TDCA) and Co-Chair: Bingming Chen, Merck
Agenda:
1. Welcome from Focus Group Chairs and Overview of the Focus Group Purpose and Goals
2. Overview of events/webinars/publications/updates since last Focus Group meeting in September 2022
3. Panel discussion: challenges and opportunities of the bioanalysis for Bro5 molecules
4. Overview of upcoming events/webinars/publications
5. Thanks and Adjourn
Modeling and Simulations Focus Group
Chair: Yuan Chen, Genentech and Co-Chair: Maria Posada, Lilly
Agenda:
1. Welcome from Focus Group Chairs and Overview of the Focus Group Purpose and Goals
2. Overview of past and upcoming events
3. Panel Discussion on expanding the M&S focus group activities beyond traditional small molecules
4. Feedback
5. Thanks and Adjourn
6:00 pm - 6:15 pm | Opening Welcome | Grand AB
Welcome Remarks
ISSX 25th North American Meeting Co-Chairs, Amit Kalgutkar, Pfizer, USA and Fatemeh Akhlaghi, Pfizer, USA
Scott Obach, ISSX President, Pfizer, Groton, Connecticut, USA
6:15 pm - 6:45 pm | History of ISSX | Grand AB
40 Year Anniversary: The Origins of ISSX by One of Its Co-Founders, Bruce Migdalof
Margaret O. James, Professor Emeritus, University of Florida, College of Pharmacy, Gainesville, Florida, USA
6:45 pm - 7:45 pm | Opening Keynote | Grand AB
Drug Metabolism: A Half-Century Plus of Progress, Continued Needs, and New Opportunities
F. Peter Guengerich, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
7:45 pm - 9:45 pm | Opening Welcome Reception | Galleria Hall
Attendee and Exhibitor Reception and Networking
All participants 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.
