The concept of using bispecific antibodies for tumor therapy has been developed more than 30 years ago with many initial struggles. However, new developments such as sophisticated molecular design and genetic engineering have helped tremendously in solving many technical challenges and created the next generation bispecific antibodies with high efficacy and safety profiles.

With many successes recently, the ‘zoo’ of bispecific antibodies now consists of more than 100 different formats, and about 80 bispecific antibodies are currently in clinical trials.

As a growing class of immunotherapies, bispecific antibodies continue to show significant and impressive therapeutic value. At the 5th Annual Immuno-Oncology Summit Europe in London, UK from March 9-12, 2020, we will focus on the challenges and solutions for bispecific development such as target selection, better understanding of their mechanism of action and their many applications for immuno-oncology therapies.

KEYNOTE PRESENTATION: Current Landscape and Outlook of Bispecific Antibody

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Roland Kontermann, PhD, Professor, Biomedical Engineering, Institute of Cell Biology and Immunology, University of Stuttgart

Bispecific antibodies have experienced a dramatic interest and growth for therapeutic applications, with more than 80 molecules in clinical development; e.g., in oncology, immuno-oncology, but also for non-oncology applications. An overview will be given on the making of bispecific antibodies and the various therapeutic concepts and applications, e.g., for dual targeting strategies, retargeting of immune effector cells, and substitution therapy by mimicking the function of natural proteins.

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Functional Screening Unlocks the Therapeutic Potential of Bispecific Antibodies

Mark Throsby, PhD, CSO, Merus NV

Case studies of clinical assets will be discussed that highlight the role of empirical functional screening. Examples will include both I-O and targeted therapies demonstrating that diverse functional readouts can be incorporated into bispecific antibodies screens.

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Selection-Based Development of a Heavy Chain-Light Chain Pairing Technology

Paul Widboom, PhD, Associate Director, Antibody Discovery, Adimab LLC

A significant challenge in the development of multivalent bispecific antibodies involves solving the “heavy chain-light chain pairing problem.” While most heavy chain-light chain pairs possess a preference for their cognate partner, noncognate mispairing occurs. Avoiding these undesired mispairs is a relevant challenge in the field of bispecific antibody manufacturing. Here we present a solution to the heavy chain-light chain problem derived from a novel selection system. This system finds mutations that improve cognate heavy chain-light chain pairing while maintaining antigen binding affinity.

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A Novel Class of Fully Human Co-Stimulatory Bispecific Antibodies for Cancer Immunotherapy

Dimitris Skokos, PhD, Director, Immunity & Inflammation, Regeneron Pharmaceuticals

T-cell activation is initiated upon binding of the T-cell receptor (TCR)/CD3 complex to peptide-MHC complexes (“signal 1”); activation is then enhanced by engagement of a second “co-stimulatory” receptor, such as the CD28 receptor on T cells binding to its cognate ligand(s) on the target cell (“signal 2”). Recently described CD3-based “bispecific antibodies” act by replacing conventional signal 1, linking T cells to tumor cells by binding a tumor-specific antigen (TSA) with one arm of the bispecific, and bridging to TCR/CD3 with the other.

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Next-Generation Bispecifics for Cancer Immunotherapy

Michelle Morrow, PhD, Vice President, Preclinical Translational Pharmacology, F-star

The use of bispecific antibodies can potentially modulate anti-tumour immune responses. Bispecific antibodies: an attractive alternative to cancer treatment combinations. F-star’s approach to create bispecific mAb². In vitro and in vivo efficacy of F-star bispecific antibodies targeting oncology pathways observed in preclinical studies.

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Bispecific Gamma Delta T Cell Engagers for Cancer Immunotherapy

Hans van der Vliet, MD, PhD, CSO, LAVA Therapeutics; Medical Oncologist, Amsterdam UMC

Vγ9Vδ2 T cells constitute the largest γδ T cell subset in human peripheral blood and are powerful anti-tumor immune effector cells that can be identified in many different tumor types. This presentation will discuss bispecific antibodies designed to engage Vγ9Vδ2 T cells and their use for cancer immunotherapy.

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Combinatorial Approaches to Enhance Bispecific Anti-Tumor Efficacy

Eric Smith, PhD, Senior Director, Bispecific Antibodies, Regeneron Pharmaceuticals

This presentation will describe Regeneron’s bispecific platform and present preclinical data on REGN4018, a clinical stage T cell engaging bispecific targeting Muc16 for solid tumor indications. In addition, status updates on Regeneron’s other clinical stage bispecific antibodies (REGN1979, REGN5458, REGN5678) will be presented as well as a discussion of new combinatorial approaches being taken to enhance bispecific anti-tumor efficacy.

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