Antibody PK/PD and ADAPT Workshop

Thursday, May 17 - Saturday, May 19, 2018
Niagara Falls, NY

This workshop has been designed to provide a detailed discussion of issues relevant to the pharmacokinetic / pharmacodynamic (PK/PD) modeling of antibody drugs, and to provide a series of “hands-on” case studies describing the development and application of mathematical models to simulate and characterize antibody PK/PD.

On this page:

Workshop Overview

Lectures will address primary determinants of antibody pharmacokinetics (PK) and pharmacodynamics (PD), the design and
implementation of pre-clinical investigations of antibody PK/PD, and state-of-the-art mathematical models to characterize and predict antibody PK and PD. Case studies, featuring use of the ADAPT program, will include application of models for antibody-ligand binding and disposition, target-mediated disposition, and physiologically-based pharmacokinetic modeling. Special emphasis is placed on discussion of the role of FcRn on the absorption, distribution, and elimination of antibodies, on the mathematical modeling of target-mediated antibody disposition, and on physiologically-based modeling of antibody pharmacokinetics. The workshop content is provided as a combination of formal lectures and informal review sessions.

Subjects that will be presented include:

  • Determinants of antibody pharmacokinetics and pharmacodynamics: mechanisms of antibody elimination, the role of
    convection in the kinetics of antibody distribution, the role of FcRn in antibody absorption, distribution, and elimination
  • Interspecies Scaling of Antibody PK: considerations and examples involving the use of allometric methods to scale protein pharmacokinetics from pre-clinical models to humans
  • Drug-drug interactions: mechanistic considerations and examples for drug-drug interactions involving monoclonal antibodies, including consideration of antibodies as perpetrators and as victims of DDI
  • Target-Mediated Antibody Disposition: modeling, implications for interspecies scaling, implications for First-in-Human studies
  • Modeling of bimolecular antibody-ligand interaction
  • Physiologically-based pharmacokinetic modeling: Incorporation of FcRn-mediated antibody transport in PBPK models, incorporation of target-mediated disposition, use of PBPK and preclinical data to predict antibody disposition in humans

Course Instructors

Joseph P. Balthasar, PhD
Dr. Balthasar is Professor of Pharmaceutical Sciences at the University at Buffalo, State University of New York and Director of the Center for Protein Therapeutics. His PK/PD modeling interests and capabilities include the development and preclinical evaluation of anti-toxin immunotherapies, the development and preclinical evaluation of anticancer immunotherapies (including immunoconjugate immunotherapies), and the development and preclinical evaluation of novel immunotherapies for humoral autoimmune conditions.

David Z. D'Argenio, PhD
David Z. D'Argenio, PhD, is Professor of Biomedical Engineering at the University of Southern California and holder of the Chonette Chair of Biomedical Technology. He is a Fellow of the American Institute for Engineering in Medicine and Biology, American Association of Pharmaceutical Sciences, International Society of Pharmacometrics, and a past member of the FDA Advisory Committee for Pharmaceutical Science and Clinical Pharmacology. Since 1985 he has served as co-director of the Biomedical and Simulations Resource (BMSR) at USC, which develops, applies and disseminates advanced modeling methods for studying biological systems, where he has also led the development of the ADAPT software for PK/PD modeling and analysis.

Donald E. Mager, PharmD, PhD
Donald Mager is Professor of Pharmaceutical Sciences at the University at Buffalo, State University of New York. He was also a Visiting Professor at the University Paris Descartes (Jan. 2007-2013). He currently serves on the Clinical Pharmacology Advisory Committee to the FDA, and as an Associate or Consulting Editor at CPT:Pharmacometrics & Systems Pharmacology, J. of Pharmacology & Experimental Therapeutics, and Pharmacology, Research & Perspectives. His research involves identifying molecular and physiological factors that control the pharmacological properties of drugs, with a focus on anti-cancer and immunomodulatory agents.

Dhaval K. Shah, PhD
Dhaval K. Shah, PhD, is Assistant Professor of Pharmaceutical Sciences at the University at Buffalo, State University of New York. His research focuses on understanding the determinants for the ADME of protein therapeutics. He is involved in the development of a platform PBPK model for biologics that can characterize and predict the pharmacokinetics of diverse protein therapeutics in several preclinical species and human. Dr. Shah also directs the discovery, development and clinical translation of novel protein therapeutics like antibody-drug conjugates and bi-specific molecules in his laboratory. His research is supported by NIH & pharmaceutical industry.

2018 Agenda

Thursday, May 17   Friday, May 18
  Saturday, May 19  
8:45 Continental Breakfast 9:00

Mathematical Modeling of Bimolecular Antibody-Antigen Interaction and ADC PKPD (Shah)

  • Review of binding kinetics (Law of Mass Action, equilibrium
    vs. non-equilibrium binding)
  • Mathematical modeling of antibody binding: Examples from
    antibodies used for immunotoxicotherapy
  • Introduction to mechanistic modeling of ADC PKPD
9:00 Case Study: Target Mediated Drug Disposition (Mager)
8:30 Introductions 10:00

Physiologically-Based PK Modeling of Mab (Balthasar)

  • Review of PBPK models
  • Application of PBPK models applied to Mab
  • Discussion of major features of PBPK models for Mab & discussion of associated physiology (convection, restriction coefficients, sites of catabolism, “two-pore formalism”,
    incorporation of specific binding, incorporation of FcRn)
9:45 Case Study: Antibody-Ligand Interaction and Disposition
(Balthasar)
9:00

Introduction to Antibody Pharmacokinetics (Balthasar)

  • Introduction to antibodies (isotypes, polyclonal vs.
    monoclonal, humanization, etc.)
  • Mechanistic determinants of antibody absorption,
    distribution, and elimination (contrasting with determinants
    of small-molecule ADME)
  • Comments on the mathematical modeling of antibody PK
  • Recent research relating to the role of FcR and mAb PK
11:00 Break 10:15 Break
11:00 Break 10:15 Break 10:30 Case Study: Physiologically-Based Pharmacokinetic
Modeling for mAb (Balthasar)
11:15

Analytical Assays for Antibodies: Implications for PK/PD Analyses (Balthasar)

  • Discussion of major types of analytical assays for monoclonal antibodies (ELISA, RIA, LC MS/MS, SPR,
    “direct” labeling)
  • Examples / case-studies
11:15

Review Module #2: Design & Analysis of a Preclinical Investigation of Antibody PK (Part 2, Balthasar)

  • Development of mechanistic mathematical models
11:15 Case Study: PKPD for Antibody Drug Conjugates (Shah)
11:40

Immunogenicity and Macromolecule PK/PD (Shah)

  • Factors associated with immunogenicity
  • Identification of host “anti-drug” antibodies
  • PK modeling
12:00 Lunch 12:00 Lunch
12:00 Lunch 1:00 Application of PK/PD Theory to Guide the Discovery and Development of New Immunotherapies (Balthasar) 1:00 Modeling Bispecific mAb PKPD (Shah)
1:00 Use of PK/PD Studies to Support Comparability Assessments of Therapeutic Proteins (Balthasar) 2:00 Background: Modeling with ADAPT (D’Argenio) 1:45 Case Study: Denosumab PKPD (Mager)
1:30

Interspecies Scaling of Antibody PK & PD (Balthasar)

  • General review of interspecies scaling
  • Considerations for scaling antibody pharmacokinetics
  • Examples / case-studies
3:15 Break 2:30 Break
2:15

Mathematical Modeling of Target-Mediated Disposition of Monoclonal Antibodies (Balthasar)

  • Introduction to TMD of Mab with examples
  • Review of mathematical models that have been applied to
    characterize Mab TMD
  • Comparison of model performance; discussion of implications for predicting Mab PK/PD
3:30

Review Module #3: Prediction of the Influence of Shed Antigen on the Distribution of Mab in Solid Tumors
(Balthasar)

  • Model building exercise
  • Simulations
2:45 Estimation Principles & Challenges for Biologics (D’Argenio)
3:30 Break 4:15

Review Module #4 (Balthasar)

  • Discussion questions and review
3:30 Case Study: Non-depleting Anti-CD4 mAb (D’Argenio)
3:45

Biologics and Drug-Drug Interactions (Balthasar)

  • Mechanisms
  • Examples / case-studies
5:00 Adjourn
4:15 Discussion / Adjourn
4:15

Review Module #1: Design & Analysis of a Preclinical Investigation of Antibody PK (Balthasar)

  • Study objectives
  • Consideration for study design
  • Assay considerations
  • Initial evaluation of data (Additional studies needed?)
  • Initial characterization of ADME (NCA vs. modeling)
  • Evaluation of NCA results
       
5:00 Adjourn        

Registration Information

Fee

Individual fee: $2500. This includes course documentation, continental breakfasts, mid-session refreshments, lunches and opening dinner. Up to 5 graduate students may enroll at a fee of $1200 (registered MS and PhD). US Government rate: $1900 (FDA and NIH employees only).

Cancellations

Cancellations with a full refund may be made until March 13, 2018. No refund is possible on cancellations received after  this  date. Substitutions may be made at any time. Please inform course secretary of any substitutions.

Course Location

The course will be held at:
The Conference and Event Center Niagara Falls
101 Old Falls Street
Niagara Falls, NY 14303, USA
Phone: (716) 278-2100
Fax: (716) 278-0008

The Conference Center is 28 minutes from the Buffalo Niagara International Airport.

Hotel Location

Sheraton at the Falls
300 Third Street
Niagara Falls, NY 14303, USA
Phone: (716) 285-3361.

The price is $124/night single and double occupancy (add $10 per person for triple and quadruple occupancy).

Hotel deadline: April 16, 2018

Questions?

Contact UB course secretary Suzette Mis at (716) 645-4831 or mis@buffalo.edu if you need assistance.