Roundtable Breakout Discussions

These interactive discussion groups are open to all attendees, speakers, sponsors, & exhibitors. Participants choose a specific breakout discussion group to join. Each group has a moderator to ensure focused discussions around key issues within the topic. This format allows participants to meet potential collaborators, share examples from their work, vet ideas with peers, and be part of a group problem-solving endeavor. The discussions provide an informal exchange of ideas and are not meant to be a corporate or specific product discussion.

Wednesday, October 16 2:45 pm

Immunogenicity Assessment and Clinical Relevance

Table 1: Recent Advances with Novel Modalities: Gene Therapy, CAR-T therapy, Peptides and More

Moderator: Jim McNally, PhD, Executive Director, Head of Research and Clinical Assays, Program Lead, CRISPR Therapeutics

• Recent data on pre-existing reactivity for AAV
• Immunogenicity assessment of novel modalities
• Application of current guidance to novel modalities
• What is your product? The vector, the expressed product?

Table 2: Strategies to Improve Drug Tolerance and Manage Interference

Moderator: Lilia Macovei, PhD, Bioanalytical Principal Investigator, Senior Scientist, Pfizer

• Dissecting strategies for managing the drug/target interferences and drug tolerance in Gene therapy programs vs LBA
• Case studies of matrix interference in ADAs and Nabs

Table 3: Individual vs. Population-Risk Assessment of Immunogenicity – Relevance for Labeling Information

Moderator: Sandra Garces, MD, PhD, Senior Medical Advisor for Immunogenicity, Global Patient Safety, Eli Lilly

• Differences between the two
• Assessing the risk of IMG at a population-level and defining the impact of IMG on the overall benefit-risk profile of the product
• How to demonstrate a causal association between the development of ADA and undesirable clinical outcomes and assess the impact and clinical relevance of those outcomes in the specific patient population
• How to define clinically useful information on IMG for labelling purposes

Table 4: Assessing Immunogenicity in Oncology Trials

Moderator: Mohamed Hassanein, PhD, Staff Scientist, Bioanalytical Sciences, Regeneron Pharmaceuticals

• Immunogenicity assessment Immune checkpoints blockers mAbs
• Challenges and solutions for evaluating NAbs of bispecifics and multi domain biologics
• Immunogenicity assessment for IO new therapeutic modalities (i.e. Oncolytic viruses, therapeutic vaccines, DNA editing vectors)
• Immunogenicity assessment for cell-based therapeutics (i.e. CAR-T, TILs)

Table 5: The Challenge of Drug- and Matrix-Interference in Immunogenicity Testing

Moderator: Weifeng Xu, PhD, Principal Scientist, Merck

• Current practice to overcome drug and matrix interference
• Case studies where desired drug tolerance cannot be achieved
• Issues with current practice of overcoming drug and matrix interference

Friday, October 18 7:30 am

Immunogenicity Prediction and Control

Table 1: Viability of Immune Tolerance Strategies for the Treatment of Human Disease

Moderator: Stephen Miller, PhD, Professor of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University

• What are the appropriate disease indications for testing tolerance therapy in initial clinical trials?
• What factors are important in developing the ideal approach for tolerance induction?
• What immune tolerance induction approaches are currently in development for disease prevention and therapy?
• What are the similarities and differences in the mechanism(s) of action by the different tolerance approaches?

Table 2: Development of Robust T Cell Response Immunogenicity Prediction Assay

Moderator: Karen Liao, MD, Investigator, GSK Associate Fellow, GlaxoSmithKline

• Selection of assay format: DC-CD4 T vs DC-PBMC, vs whole PBMC, vs CD8 depleted PBMC assay. Pros and cons for each format?
• Considerations for assay controls, assay variation and assay acceptance criteria. How to treat replicates? Does replicate %CV apply to the low frequent Ag specific CD4 detection?
• Data interpretation: Positive response criteria and rank responses
• How do T cell responses correlate to the clinical immunogenicity? Is the response rate or the strength of response more relevant? Any magic number of CD4 T cell response for high immunogenicity risk clinically?

Table 3: Molecular Characterization of Immunogenicity

Moderator: Brandon DeKosky, PhD, Assistant Professor, The University of Kansas

• How to rescue immunogenic lead candidates
• Understanding the mechanisms of epitope spreading
• Advantageous vs. benign vs. harmful immunogenicity
• Optimal monitoring and assay development for immunogenicity analysis

Table 4: Practical Application of Prediction Tools and the T Cell Response

Moderator: Bernard Maillere, PhD, Research Director, Immunology, CEA

• What methods are available for preclinical assessment of immunogenicity?
• What are the principles, outcomes and value of each method?
• How many formats are there? What are their respective advantages?
• How to combine the information provided by the prediction tools with that coming from other factors contributing to immunogenicity

Table 5: Implementing an Immunogenicity Risk Assessment Strategy from Discovery to Preclinical to Clinical and Beyond

Moderator: Vibha Jawa, PhD, Director, Predictive and Clinical Immunogenicity, Pharmacokinetics, Pharmacometrics and Drug Modeling Group, Merck

Optimizing Bioassays for Biologics

Table 6: What is Parallelism, and Why is it so Important?

Moderator: Steven Walfish, MBA, Principal Scientific Liaison, USP

• Is this the same as dilutional similarity?
• Why is the F-test outdated?
• What happens if my curves are not parallel?
• Discuss your experience with parallelism testing

Table 7: Validity Criteria Selection for a Bioassay

Moderators: Thomas Little, PhD, President and CEO, Bioassay Sciences, Thomas A. Little Consulting
Daniel Harding, Principal Consultant, Bioassay Sciences

• Selection of Systems Suitability and alternatives
• Validity Criteria and Limits
  • Positive Control
  • Negative Control
  • Curve Parameters
  • R2, RMSE
  • RP Delta
  • Curve Parameter Ratios
  • Equivalence Tests
  • F-Tests