Topic 1:

The Optimal ADA Assay by using Model-Informed Assay Development:  Advancements in ADA-Drug Immune Complex Formation in Clinical Samples: Impact of ADA-Drug complexes formation of different sizes on PK and Biodistribution; Issues with current lack of information on ADA-drug complexes size distribution; Immune complexes effects on bioanalytical methods and limitations of the use of artificially prepared QCs for assay development and validation.

Topic 2:

Recent Advancements in Cut Point Calculation by Application of Mixed Effect Modeling: Random Effect Modeling (REM) with one or more fixed effect as statistical approach for CP; Alleviating issue of validation and in-study cut point experiment design differences; Identification of variance components in ADA data in balanced CP experiment design; Controlling variability within the data set resulting in limited or no outlier removal.

Topic 3:

NAb Monitoring Strategy during clinical development to evaluate interaction therapeutic/target and impact on efficacy: Latest considerations on Cell-Based Assays for Neutralizing Antibody (CBA for NAb); Preferred application of CBA to reflect MoA; Overcoming CBA challenges, poor sensitivity & drug tolerance, variability by optimization of Positive Control (PC), assay parameters, stimulation concentration, incubation time; Use of competitive LBA when CBA are not feasible.

Topic 4:

ADA Monitoring Strategy for Repetitive High Doses of Biotherapeutics: How to efficiently integrate scientific, technical, and regulatory aspects in a thorough assessment of ADA frequency for safety & efficacy; Using ADA domain mapping as essential tool for understanding immune responses to complex biotherapeutics, bi- and tri-specific antibodies and therapeutic protein conjugates; Evaluating the bioanalytical performance of Cell-Based Assays for Neutralizing Antibody (CBA for NAb).

Topic 5:

State-of-the-art Strategies for Performing (or not) ADA Retrospective Comparability Studies: What's the value of running these studies? Challenges, best design, criteria to apply ADA comparability studies; Dealing with absence of ADA comparability studies in current filing packages and considerations to demonstrate assay comparability by other means; How to deal with methods implemented in China with Cut Point validated for a different population?

Topic 6:

Latest Approaches for Reporting Immunogenicity Data from Different Laboratories using Validated Methods but with Different ADA Incidences:  What are the expectations regarding ADA validation criteria and merging results from different labs for a single clinical study? What are current practices for Cross-validation between Laboratories, and what is acceptable for reporting data from different labs? Implications on ADA method development, validation and sample testing.

Topic 7:

Unique Approach for ADA Assay Cross Validation by using Flow Chart to minimize the number of assays needed: Why and when do we need to perform cross-validation and impact on pulling result from different studies? What are the available Regulatory Expectations on immunogenicity Cross Validation from different agencies worldwide? Decision tree when cross validation is needed and the challenges with use of incurred samples. 

Topic 8:

Understanding the Clinical Immunogenicity of Novel Insulin Analog: Use of structural engineering, amino acid substitutions, use of a single chain insulin, and fusion of the single chain insulin to Fc to minimize the immunogenicity risk. ADA Assay to detect in treated participants treatment-emergent ADA; Consideration on participants with and without pre-existing ADA to evaluate ADA incidence and their clinically effect on efficacy.

Topic 9:

Unconventional Approaches for ADA Assay to Assess Bispecific Antibodies (BsAb) Immunogenicity:  Next generation mAb targeting two antigens or epitopes with synergistic features producing more significant treatment effects; BsAb complex molecule structure, target biology and clinical development plan; Current efforts for BsAb immunogenicity assessment in the clinic; Evolution of bioanalytical strategy for BsAb to support the progression of BsAb development.

Topic 10:

Challenges in Assessing Immunogenicity for Next ADC Generation: Significant number of ADC approved & in development; ADC Immunogenicity has gained increased attention from Regulatory Agencies; Increased potential of immunogenicity risk for Next ADC Generation; Issues with high pre-existing response ADC domains or target mediated response for clinically meaningful immunogenicity assessment; Proposed New Strategies of ADA Measurement and impacts the immunogenicity.

Topic 11:

Importance to understand the Immunogenicity Risk of Novel "Immunopotentiating" ADC: Impact of differences from regular IgG by sequence and/or conformation in creating neoepitopes recognized by preexisting ADA; novel unnatural formats, bispecifics, probodies, non-IgG scaffolds combined with toxic payloads, immune-stimulators, protein-degraders, dual payloads; Analysis of preclinical Immunogenicity and its potential correlation with clinical immunogenicity to help in selection of right ADC for clinical development.

Topic 12:

Automated Strategic Approaches for Rapid Immunogenicity Analysis for Challenging Biotherapeutics: Immunogenicity testing as potential barrier to expediting clinical study timelines due to ADA/NAb Assay complexity and multi-tiered testing strategy; ADA singlicate sample testing and automated assay from validation to virtual application against a large clinical data set. When do we want to compress tiers? How would singlicate be used for titer or S/N?

Topic 13:

The Elimination of Immunogenicity Tier 2 & Tier 3 Titer Testing and Labeling Considerations!  Evaluation of studies interpreting clinical impact comparing S/N use in lieu of titer for biotherapeutics with low and high immunogenicity incidence and interpretation using S/N; Eliminating confirmatory assay and statistical Cut Points for lower risk molecules; Considerations on S/N use for biotherapeutics when different levels of pre-existing ADA observed.

Topic 14:

Challenging the Current Paradigms for Immunogenicity Testing by Focusing on Science rather than just Workload Reduction: Major downsides in omitting the Confirmatory Tier; Advantages of using S/N and singlicate analysis for immunogenicity testing; Use of clinical data to show  non-inferiority of S/N vs titers and advantages for assessing the impact of ADA on PK; Major consequences to base drug tolerance on immunogenicity risk.

Topic 15:

Importance of Immunogenicity observed in Cyno Studies to predict Clinical Immunogenicity Risk:  Consideration on the correlation between cyno and clinical immunogenicity for many therapeutic; Can a rapid and robust immune response in Cynos be a warning sign for clinical immunogenicity? Widely held Perception that Cyno ADA does not translate into what occurs in the clinic is not always a correct interpretation.

2025 White Paper on Biotherapeutics Immunogenicity Assessment & Clinical Relevance - Latest Advances, Challenges and Solutions from Internationally Recognized Key Opinion Leaders

Consensus & Conclusions on Biotherapeutics Immunogenicity Assessment & Clinical Relevance - Latest Advances, Challenges and Solutions from Internationally Recognized Key Opinion Leaders for 2025 White Paper

Panel Discussion with All the Regulators:

Have an Open Dialogue with the Regulators including US FDA, UK MHRA, EU EMA, Health Canada, and Japan MHLW
Ask the Regulators any Questions You Have on Immunogenicity of Biotherapeutics and Hear Their Feedbacks on Submitted Studies and Inspections/Audits Outcomes