Immunogenicity Assessment & Clinical Relevance

Assay Strategy for Meaningful Evaluation

October 4 - 5, 2022 ALL TIMES EDT

This year's Immunogenicity Summit brings the FDA together with leading industry and academic experts to discuss the development, application, and validation of immunogenicity assays. Learn how to manage drug and target interference and tolerance, understand the impact of pre-existing antibodies, and interpret the clinical significance of assay data. Novel modalities including cell and gene therapies are posing new challenges to the industry, all of which will be discussed in-depth at this meeting.

Tuesday, October 4

Registration and Morning Coffee (Arlington Foyer)7:00 am


ROOM LOCATION: Arlington Salon V + VI

8:25 am

Chairperson's Opening Remarks

Boris Gorovits, PhD, Vice President, Bioanalytical & Non-Clinical Biomarkers, Sana Biotechnology

8:30 am

Evaluation of Immunity against AAV-Based Gene Therapy Modalities

Boris Gorovits, PhD, Vice President, Bioanalytical & Non-Clinical Biomarkers, Sana Biotechnology

Immune response against AAV-based viral delivery gene therapy products has a strong potential to impact safety and efficacy of the treatment. Pre- and post-treatment innate and adaptive responses have been investigated to determine and understand correlation with observed clinical signals. The presentation will focus on current industry experience related to methodologies applied to determine anti-GTx immunity. Recommendations generated during industry-wide conversations will be reviewed and discussed.

9:00 am

Overcoming Unique Bioanalytical Challenges Associated with Anti-Drug Antibody Assessment Supporting AAV Gene Therapy Clinical Trials

Liching Cao, Senior Director, Bioanalytical Operations, Sangamo Therapeutics

AAV gene therapy products involve complex and extensive immunogenicity assessment as these products are multicomponent. Challenges of immunogenicity assessment specific to gene therapy are related to the immune responses against these individual components, various modes of action for neutralizing antibodies, and the extent of immunogenicity assessment needed at different stages of clinical development. Case studies for developing antibody assays and strategies to overcome assay development challenges will be presented.

9:30 am

Cellular Immunogenicity Assessment for Advanced Modalities

Jim McNally, PhD, CSO, BioAgilytix

Cell and Gene Therapy drug development has led to an expanded interest in cellular immunogenicity as part of regulated bioanalysis.  Flow cytometry and ELISpot are playing a much larger role in the characterization of the patient's immune response to these therapies and leveraging these tools leads to a number of new challenges around sample collection, storage and shipment logistics and complex multiparameter analyses which will be discussed in this talk.

10:00 am Using Random and Fixed Effects Modeling for a More Accurate Cut Point Determination

Cheikh Kane, Senior Director BioPharma, KCAS Bioanalytical and Biomarker Services

Stephanie Pasas-Farmer, President and Founder, Ariadne Software LLC

ADA cut point (CP) calculation assesses the biological variance of a drug naïve population and confirms the presence of ADA after treatment in the clinic. Of multiple approaches to calculate CP, the traditional approach removes outliers, whereas a modeled approach (e.g. random effect models (REM)) retains all population data while modeling random and known sources of variance. Using case studies, we evaluate REM and propose when and how to use it.

Coffee Break in the Exhibit Hall with Poster Viewing (Arlington Salon IV)10:30 am



Simultaneously Engineering Protein Molecules for Increased Efficacy and Lower Immunogenicity

Wojciech Jankowski, PhD, Commissioner’s Fellow, CBER, FDA

Engineering therapeutic proteins for improved clinical outcomes is now routine. Introduction of neo-sequences can however elicit immune response to the engineered protein-therapeutic (immunogenicity), which is an important safety concern. The potential consequences of immunogenicity range from loss in quality life to a life-threatening situation. In my talk I will discuss emerging trends in protein engineering that can allow the design of proteins with improved efficacy and lower immunogenicity.

11:40 am Immunogenicity Assessment in the Age of New Drug Modalities

Rafiq Islam, Vice President, Bioanalysis and Biomarkers, Amador Bioscience

As the diversity and complexity of therapeutic modalities increases, our bioanalytical toolbox for the assessment of immunogenicity needs to be expanded.  This presentation focuses on the challenges and solutions associated with complex drug modalities such as nucleic acid-based therapies, multi-domain therapies, cell and gene therapies, etc. Case studies outlining best practices for method selection and validation are presented as well as a future perspective to address challenges associated with immunogenicity assessment.

12:10 pmEnjoy Lunch on Your Own

Coffee and Dessert Break in the Exhibit Hall with Poster Viewing (Arlington Salon IV)1:10 pm


1:50 pm

Chairperson's Remarks

Mauricio Maia, PhD, Senior Principal Scientist, Genentech

1:55 pm

How to Support Filing and the Clinic with Immunogenicity Testing: Unravelling the Impact of the Immune Response to Therapeutic mAbs

Karien Bloem, PhD, Senior Scientist, Bioanalysis, Sanquin Diagnostic Services

Treatment of patients with mAbs generates varying levels of ADA. To gain proper insight into the clinically-relevant effect of ADA development we have characterized the immune response in patients in the post-approval clinical setting for titers, temporal patterns, isotype (IgM, IgG1-4), anti-idiotype characterization, and ADA detection using different assays. Depending on the purpose, alternative methods could be better suited for the detection of ADA than the standard bridging assays.

2:25 pm

Immunogenicity Profile of the Port Delivery System with Ranibizumab in Patients with nAMD

Mauricio Maia, PhD, Senior Principal Scientist, Genentech

What is the immunogenicity profile of the Port Delivery System with ranibizumab (PDS) and how does it compare with that of monthly intravitreal (ITV) ranibizumab 0.5 mg injections? The immunogenicity profile of intravitreal ranibizumab 0.5 mg is well established. Incidences of anti-drug antibodies (ADAs) are low, and within a relatively narrow range of values (1–9%), and ADAs do not appear to impact safety, PK, or treatment effects. We will describe the PDS clinical immunogenicity profile and the potential impact of ADAs on visual outcomes, PK, and safety. Bioanalytical methods used in those studies will also be described.

Breakout Discussions2:55 pm

Breakout discussions provide an opportunity to discuss a focused topic with peers from around the world in an open, collegial setting. Select from the list of topics available and join the moderated discussion to share ideas, gain insights, establish collaborations or commiserate about persistent challenges. Please visit the breakout discussions page on the conference website for a complete listing of topics and descriptions.


AAV-Based Gene Therapy Modalities – IN-PERSON ONLY

Boris Gorovits, PhD, Vice President, Bioanalytical & Non-Clinical Biomarkers, Sana Biotechnology

  • What is the current industry experience related to methodologies to determine anti-GTx immunity? 
  • Value and main challenges related to harmonization of anti-GTx assays
  • What are the recommendations generated during industry-wide conversations?

Immunogenicity of CAR T Therapies – IN-PERSON ONLY

Alexander Kozhich, PhD, Director, Bristol Myers Squibb Co.

  • Immunogenicity risk assessment
  • What is relevant – humoral or/and cellular immunogenicity 
  • Bioanalytical strategy and methods​

Strategies to Improve Drug Tolerance and Manage Interference – IN-PERSON ONLY

Arkadeep Sinha, PhD, Principal Scientist, EMD Serono

  • New techniques for improving drug tolerance/target interference
  • Effect of drug tolerance mitigation strategies on cut point factors through reduced variability of naïve sample responses
  • Target selection in the face of glycosylation

Clinical Relevance of ADA – IN-PERSON ONLY

Tatyana Yun, PhD, Senior Scientist, Merck

  • Cost of developing assays and new techniques
  • Collecting good data
  • Detecting ADA 
  • Feedback from the FDA

Refreshment Break in the Exhibit Hall with Poster Viewing (Arlington Salon IV)3:45 pm


4:25 pm

Prior Therapy Interference in a Bispecific NAb Assay and Possible Mitigation Strategy

Susan Irvin, PhD, Staff Scientist, Bioanalytical Strategy, Regeneron

Cell-based assays (CBA) for NAb are notoriously challenging: drug and soluble targets can generate false-positive/negative results even at low concentrations. In a CD20xCD3 bispecific CBA, prior anti-CD20 therapy (e.g., rituximab) was also shown to interfere. This was mitigated by addition of blocking mAbs, but each anti-CD20 therapy requires specific blockers. This highlights challenges with target-based NAb assays, both from exogenous therapies and endogenous anti-target antibodies (e.g., infectious disease).

4:55 pm

Taming a Tough Positive Control mAb for Neutralization Ab Assay by Utilizing a Surface Plasmon Resonance Tool

Tatyana Yun, PhD, Senior Scientist, Merck

5:25 pm

Immunogenicity Pitfalls and Strategic Ladders in Development of Therapeutic Proteins

Amy Rosenberg, MD, Senior Director of Immunology and Protein Therapeutics, Epivax

Welcome Reception in the Exhibit Hall with Poster Viewing (Arlington Salon IV)5:55 pm

Close of Day7:00 pm

Wednesday, October 5

Registration and Morning Coffee (Arlington Foyer)7:30 am


ROOM LOCATION: Arlington Salon V + VI

7:55 am

Chairperson's Remarks

Jenny Valentine, PhD, Staff Scientist, Bioanalytical Sciences, Regeneron


Host Immune Response to SARS-CoV-2 and Its Implications for Long COVID

Saurabh Mehandru, Professor, Vice Chair of Research, Division of Gastroenterology, Icahn School of Medicine at Mount Sinai

The world continues to contend with successive waves of coronavirus disease 2019 (COVID-19), fueled by the emergence of viral variants. At the same time, persistent, prolonged, and often debilitating sequelae are increasingly recognized in convalescent individuals, named ‘post-COVID-19 syndrome’ or ‘long-haul COVID’. Clinical symptomatology includes fatigue, malaise, dyspnea, defects in memory and concentration, and a variety of neuropsychiatric syndromes as the major manifestations, and several organ systems can be involved. The underlying pathophysiological mechanisms are poorly understood at present. We will discuss organ-specific sequelae of post-COVID-19 syndromes and examine the underlying pathophysiological mechanisms available so far, elaborating on persistent inflammation, induced autoimmunity, and putative viral reservoirs.


8:30 am

Immunogenicity Assessment with Pre-Existing Antibodies – Mitigation Strategies for ADA and NAb Bioanalysis

Inna Vainshtein, Senior Director, Bioanalytics, Exelixis

Immunogenicity assessment is a critical part in drug development of biotherapeutics as anti-drug antibodies may impact drug PK, efficacy, and safety. Pre-existing or cross-reactive antibodies in drug naïve subjects may elevate assay cut points leading to inaccurate reporting of immunogenicity. In this presentation, we will discuss a case study with high prevalent pre-existing antibodies and approaches applied to ADA and NAb methods to overcome this challenge conferring accurate assessment of immunogenicity.

9:00 am

Bioanalytical Considerations for Immunogenicity of Immune Effector Cell Therapies

Alexander Kozhich, PhD, Director, Bristol Myers Squibb Co.

T cells engineered to target patient tumors proved to be extremely powerful addition to anti-cancer armamentarium. Expansion and long-term survival of engineered T cells are crucial for cancer therapy success. Patient’s immune response, both humoral and cellular may adversely affect T cells persistence. Therefore, ADA and cellular immunogenicity assays are needed to understand patient immune response and its effect on cellular therapy success. This presentation will share learnings gathered from the literature and experience, on factors that should be considered when setting an immunogenicity bioanalytical strategy.

Coffee Break in the Exhibit Hall with Poster Viewing (Arlington Salon IV)9:30 am

10:10 am

Navigating Immunogenicity Assessments for Multi-Domain Antibodies

Arkadeep Sinha, PhD, Principal Scientist, EMD Serono

Multi-domain molecules bring in added complexities during the development and validation of ADA assays. In this presentation, we will walk through a case study for a bispecific T cell engager that required multiple optimizations to achieve desired drug tolerance while avoiding a low screening cut-point factor and realizing confirmation with individual domains of the drug.

10:40 am

Population-Specific Cut Points in Oncology: Does Every Tumor Type Really Need a Different Cut Point?

Jenny Valentine, PhD, Staff Scientist, Bioanalytical Sciences, Regeneron

Current regulatory guidance states that ADA assay cut points need to be verified for appropriateness in different populations. For a mAb therapeutic, assay responses from over two thousand samples from seven different cancer types were compared using accepted statistical methods. Study-specific cut points may be required in some diseases like immunology and inflammation; however, based on our analysis, in-study cut points were not required for each new oncology disease indication.


11:10 am

The HLA-II Immunopeptidome of Endogenous and Therapeutic Incretin Peptides: From Tolerance to Immunogenicity

Robert Siegel, PhD, Research Fellow, Laboratory for Experimental Medicine, Eli Lilly and Company

MHC-associated Peptide Proteomics (MAPPs) allows the sequences presented for immune surveillance after natural processing in antigen presenting cells to be precisely defined. This technique has been primarily applied to understanding the risk of immunogenicity with therapeutic antibodies. This presentation will present findings from therapeutic peptides and compare those results to those obtained with endogenous incretin peptides. The impact of non-natural amino acids and acylation will be discussed.

Close of Conference11:40 am