MAIN CONFERENCE

WEDNESDAY, APRIL 8

7:30am   Registration and Morning Coffee

ASSESSMENT AND DEVELOPMENT OF ASSAYS FOR IMMUNOGENICITY

• Screening
• Confirmatory Assays
• Strategies to Address Drug Interference

8:30         Chairperson’s Opening Remarks

Lawrence N. Callahan, Ph.D., Chemist, Office of the Commissioner, FDA

9:10         Next Generation Biologics: Deimmunization and Tolerance Induction

Anne S. De Groot, M.D., CEO/CSO EpiVax, Inc.; Professor and Director, Institute for Immunology and Informatics, University of Rhode Island; Pediatric Infectious Disease, Brown University Medical School

We have developed and validated a set of tools with three primary applications to drug development: 1) ranking of the overall immunogenicity of proteins according to their putative T-cell epitope content, 2) analysis of the protein for clusters of T-cell epitopes (the underlying cause of immunogenicity), and 3) pinpointing of key residues that can be strategically altered to disrupt those epitope clusters. In addition, we have identified a set of putative natural T regulatory epitopes (Tregitopes) which, when co-administered with an antigen, cause the expansion of antigen-specific adaptive. We have now confirmed that co-administration of Tregitopes with a range of proteins (such as Ovalbumin, Botulinum toxin peptides, Dust mite antigen, flu epitopes) in vitro and in vivo leads to suppression of T cell and antibody responses to the test antigens. The mechanism of suppression appears to be due to the induction of antigen-specific adaptive tolerance induction (De Groot AS et al. Activation of natural regulatory T cells by IgG Fc-derived Peptide “Tregitopes” Blood (2008) 112: 3303).  

9:40         Immunogenicity Assay Cut-point(s)

Eric Wakshull, Ph.D., Senior Scientist & Group Leader, Bioanalytical R&D, Genentech,  Inc.

Recent guidance white papers have recommended a risk-based approach to developing immunogenicity strategies and assays in support of protein therapeutic pre-clinical and clinical development.  The current recommended approach for establishing a cut-point for screening assays based upon population variability and a target 5% untreated positive rate for drug-naïve samples has been extended to include methods for determining cut-points for confirmatory and titration assays.  The basis for unified approach will be described for all three cut-points, and examples provided.  We feel this consistent approach provides an unbiased cut-point at each step of sample analysis and in particular helps solve the common observation of titer samples not crossing their cutpoint.

10:10       Coffee Break in the Exhibit Hall

11:10       Immunogenicity and T cell responses:  What Can We Learn from Monitoring T-Cell Responses to Autoantigens?

Vicki Seyfert Margolis, Ph.D., Chief Scientific Officer, Immune Tolerance Network

Due to very low frequencies of autoantigen-specific T cells, their detection may be problematic and requires very sensitive methods for monitoring various cell functions. We developed and optimized conditions for an Elispot assay that enables us to monitor responses to autoantigens in Type 1 Diabetes  and Multiple Sclerosis. This assay will be introduced for monitoring T-cell immunogenicity responses.

11:40  Adverse Reactions to Biologics: Accurate and Quantitative Measurement of Specific Antibodies

Jörgen Dahlström, Ph.D., Phadia AB

Phadia has 40 years of experience in quantitative measurement of specific antibodies. With a yearly production of 70 million tests Phadias ImmunoCAP^TM technology has a proven track-record with high sensitivity, user independent results, regulatory approval and long term stability making it well suited for measuring specific antibodies to biologics in clinical development.
                                                                                                          

                                                                                                                                                                            

Sponsored by
 

12:10 Immunogenicity and Cell Based Assays on the Meso Scale Discovery (MSD) Platform

Neeta Shenoy, Ph.D., Scientist, Meso Scale Discovery

Meso Scale Discovery offers significant advantages for the rapid development and robust implementation of immunogenicity assays in preclinical and clinical settings to detect and characterize antibodies produced in response to biological therapeutics. High sensitivity, broad dynamic range and tolerance to free drug, along with reduced matrix effects and a simplified workflow renders the platform ideally suited to address the challenges of immunogenicity assays. MSD also provides solutions for cell based assays including NAb (neutralizing antibody) assays. Cell based assays on the MSD platform can range from quantitation of secreted proteins such as cytokines, monitoring changes in receptor phosphorylation status or modulation of one or more intracellular markers, to characterizing interactions between proteins and cell surface receptors.

12:40 Luncheon Presentation II (Opportunity Available)

1:10 Break

1:30 Risk Assessment of Immunogenicity and Clinical Expectations

Deborah Finco-Kent, Ph.D., Immunogenicity Lead, Drug Safety Research & Development, Pfizer Inc. 

This talk will provide some representative nonclinical and clinical case studies with several types of biological therapeutics. Each case study will include a discussion regarding risk assessment as it relates to immunogenicity, Immunogenicity assessment plans for the particular program and regulatory feedback with respect to immunogenicity assessment.

2:00 Problem Solving Break-out Session: Drafting a Risk-based Immunogenicity Plan for a New Biologic Candidate

Facilitators:

Table 5

Darshana Jani, Senior Associate Scientist, Biogen Idec Inc and Jaya Goyal, Associate Director, Clinical Science & Technology, Biogen Idec Inc.

Table 6

Eric Wakshull, Ph.D., Senior Scientist & Group Leader, Bioanalytical R&D, Genentech, Inc.

Table 7

Bonita Rup, Assistant Vice President, Protein Bioanalysis, Bioanalytical R&D, Drug Safety and Metabolism, Wyeth Research

Table 8

Deborah Finco-Kent, Ph.D., Immunogenicity Lead, Drug Safety Research & Development, Pfizer Inc.

3:05 Refreshment Break in the Exhibit Hall

PRECLINICAL ASSESSMENT OF IMMUNOGENICITY

3:45 Chairperson’s Remarks

Joy Cavagnaro, Ph.D., DABT, RAC, President, Access BIO LC

3:50 The Value of Immunogenicity Assessment in Preclinical Development

Joy Cavagnaro, Ph.D., DABT, RAC, President, Access BIO LC

Since administration of human proteins to animals is expected to eliciting an immunological response the primary objective of assessing preclinical immunogenicity is to better define the PK/PD profile, exposure margins and estimates of toxicity which may be impacted by antidrug antibodies. Animal models can also be useful in assessing relative immunogenicity and in validating de-immunization strategies.

4:20 A Regulatory Perspective

Lawrence N. Callahan, Ph.D., Chemist, Office of the Commissioner, FDA

4:50 Networking Cocktail Reception in the Exhibit Hall

6:00 Close of Day