SC1: Preclinical and Clinical Assessment of Immunogenicity: Multidomain Therapeutics and New Modalities, Including Gene Therapy and CAR T
SUNDAY, APRIL 29, 2018
MORNING 10:00 AM - 1:00 PM
10:00am Chairperson’s Opening Remarks
Darshana Jani, M.Sc., Associate Director, Global Lead Biologics, Clinical Assay Group, Global Product Development, Pfizer, Inc
10:10 Challenges and Strategies for Development of Clinical and Non-Clinical Immunogenicity Assays for Multiple Domain Biotherapeutics Including ADCs and Bispecific Mab/ADCs
Seema Kumar, PhD, Associate Director, Quantitative Pharmacology & Drug Disposition (QPD), R&D Global Early Development (GED), EMD Serono, A business of Merck KGaA, Darmstadt, Germany
As with other biologics, multi-domain biologics (MDBs) may also evoke immunogenicity response, and hence require immunogenicity monitoring and testing strategies driven by thorough immunogenicity risk assessment. The presentation will highlight some of the challenges associated with immunogenicity assays for MDBs (ADCs and bispecific mAbs/ADCs) and the mitigation strategies that could be used to address such challenges.
10:50 Immunogenicity Assessment in Support of Gene Therapy Program-Use of ELISPOT Technology
Magdalena Tary-Lehmann, MD, PhD, Chief Scientific Officer, Cellular Technology Limited (CTL) and Adjunct Associate Professor of Pathology Case Western Reserve University (CWRU)
11:30 Refreshment break
11:40 Impact of Immunogenicity on PK/PD relationships of Biologics
Ravi Shankar Prasad Singh, PhD, Associate Director, Clinical Pharmacology, Pfizer Inc.
Understanding the relationship between pharmacokinetics (PK) and pharmacodynamics (PD) is vital in decision making at different stages of the drug development. By its complex structures, biologics exhibit unique PK-PD characteristics. Administration of these biologics can cause the formation of anti-drug antibodies (ADA) and neutralizing antibodies (NAB) impacting their PK or PD. Case studies unraveling the impact of ADA/NAB on PK and PK/PD relationships will be discussed.
12:20 ADA testing and insights into hypersensitivity
M. Benjamin Hock, PhD, Director of Immunogenicity, BioMarin Pharmaceutical Inc.
Identification of anaphylaxis based on clinical symptoms, rather than immunologic mechanism, was put in place to help clinicians rapidly identify and select the best acute treatment options for anaphylaxis. Historically, the term anaphylaxis was reserved for IgE-mediated hypersensitivity events and anaphylactoid was used to describe similar clinical events that were non-IgE mediated. However, some non-IgE hypersensitivity events are now being caught under the broad term of anaphylaxis, complicating the processes of determining immunological mechanism and discerning which patients are at higher risk. This presentation will focus on deciphering the immunological mechanism of anaphylaxis and the implications on patient management.
1:00 Close of Short Course
Biographies:
Darshana Jani, M.Sc., Associate Director, Global Lead Biologics, Clinical Assay Group, Global Product Development, Pfizer, Inc
Darshana Jani has nearly 25 years of practice in the academic and biotechnology field. Throughout her tenure at Genzyme, Medimmune, BiogenIdec until present employment as Senior Manager at Pfizer she has supported clinical and pre-clinical trials, in addition to post marketing studies inclusive of Safety, Immunogenicity, PK, Efficacy, and Biomarker analysis. Darshana has risen from the ranks, at the outset developing and applying boianalytical methods, while assuming numerous responsibilities germane to regulatory compliance of the validation and application of group procedure. She has guided bioanalytical lab groups, held responsible for overseeing all phases of drug recovery and development; a task which incorporated product characterization, potency determination, immunogenicity testing, as well as surrogate maker discovery.
Seema Kumar, PhD, Associate Director, Quantitative Pharmacology & Drug Disposition (QPD), R&D Global Early Development (GED), EMD Serono, A business of Merck KGaA, Darmstadt, Germany
Seema Kumar is an Associate Director and DMPK senior project representative at EMD Serono Inc. (a business of Merck KGaA, Germany). In her role, Dr. Kumar manages overall nonclinical drug disposition contribution to NBE projects including PK, ADME, translational modeling & simulations, bioanalysis (BA), immunogenicity strategy, and scientific oversight of outsourced large molecule programs through the different discovery and development stages. Previously, Dr. Kumar led regulated BA group in Pharmacokinetics and Dynamics Metabolism (PDM-NBE) department at Pfizer. The group provided regulated (GLP/GCP) BA support including assay development, validation and sample analysis for the Pharmacokinetics (PK) and immunogenicity (ADA and Nab) assessments for pre-clinical and clinical development of Pfizer’s large molecule programs. Dr. Kumar also provided oversight to Core Automation Team (CAT) engaged in automated large-molecule bioanalysis using Hamilton robotic liquid handlers. Prior to joining Pfizer, Dr. Kumar had served at roles of increasing responsibility as Director of Quality Control and Director of CLIA certified Clinical Bioanalytical Lab at XBiotech USA Inc. Dr. Kumar holds a Ph.D. in Biophysical Chemistry from Johns Hopkins University and has published several publications in peer-reviewed journals and contributed to several book chapters. Dr. Kumar sits in Advisory Board of scientific meetings, and has also given numerous talks in various national and international scientific conferences and meetings. Dr. Kumar has a special interest in Pharmacokinetics and Drug Disposition of ADCs.
Magdalena Tary-Lehmann, MD, PhD, Chief Scientific Officer, Cellular Technology Limited (CTL) and Adjunct Associate Professor of Pathology Case Western Reserve University (CWRU)
Dr. Magdalena Tary-Lehmann is Co-Founding Scientist and Chief Scientific Officer for Cellular Technology Limited (CTL). Dr. Tary-Lehmann received her M.D. and Ph.D., both from the University of Tübingen, Germany. Her postdoctoral training in Immunology was at the University of California, Los Angeles. She moved thereafter to Case Western Reserve University, where she was awarded tenure and appointed as Associate Professor in the Department of Pathology. As Chief Scientific Officer for CTL she oversees the performance of immunology assays in CTL’s GCP, GLP- and CLIA compliant contract laboratory for various pharmaceutical and biotechnology clients.
Ravi Shankar Prasad Singh, PhD, Associate Director, Clinical Pharmacology, Pfizer Inc.
Ravi Singh is currently working as a Clinical Pharmacology Lead at Pfizer. He is leading the development of various projects in biologics as well as small molecules in inflammation and immunology in different phases of clinical development. Before Pfizer, he worked at Abbvie, where he was Clinical Pharmacology Lead for Humira for IBD indications. Prior to moving to Clinical Pharmacology, he also worked in Pharmacokinetics and Drug Metabolism and Bioanalysis in India at Central Drug Research Institute, and Dr. Reddy’s lab. After completing his PhD at the University of Saskatchewan, Canada, he joined as Post-Doctoral Associate at the University of Florida. Over the years of his experience, he worked on understanding PK/PD in different therapeutic areas including immunology, oncology, anti-infectives and HCV. He has more than 25 international publications in peer reviewed journals and has authored four book chapters. He has presented his research work in several international conferences and his work has received several awards.
M. Benjamin Hock, PhD, Director of Immunogenicity, BioMarin Pharmaceutical Inc.
Ben joined the clinical immunology group at Amgen in 2010. He began at the bench developing and validating immunoassay methods. In 2014 he transitioned to product strategy, interpretation, and reporting. Ben joined the Immunogenicity Assessment group at BioMarin in 2017. Throughout his immunogenicity career, Ben has focused on the relationship between specific bioanalytical methods, and the clinically-relevant questions/hypotheses those methods are designed to address.