Bispecific Antibodies
In this chapter we aim at describing a new class of biologics in development for rheumatoid arthritis (RA), bispecific antibodies (bsAbs). These recognize two different specificities, and in most cases targets, as implied in their name. These bring about
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Introduction In this chapter we aim at describing a new class of biologics in development for rheumatoid arthritis (RA), bispecific antibodies (bsAbs). These recognize two different specificities, and in most cases targets, as implied in their name. These bring about a series of interesting questions related to target selection, potential mode of action, pharmacokinetics (PK), and whether their development differs from classical biologics. BsAb is a very dynamic field, and therefore it was not possible to review all preclinical developments in inflammatory diseases and RA in details here. As we feel a look at where bispecific antibodies have evolved from is instructive, we start this chapter with some of the main mode of actions and targets of biologics registered for RA, including combination of biologics which were tested in the clinic. We then address pathway and target selection and go over a series of points to consider where bsAbs may require special attention when compared to classical biologics for development. Related to mode of action and target is the selection of the right molecular format. We provide an overview on bsAb formats and then go more specifically over those used in molecules in development for RA and some inflammatory diseases. Finally, we provide an outlook on where this field might develop in the coming years.
A.C. Tissot (*) • U. Brinkmann Large Molecule Research, Roche Pharma Research & Early Development, Roche Innovation Center Munich, Roche Diagnostics GmbH, Nonnenwald 2, 82377 Penzberg, Germany e-mail: [email protected] © Springer International Publishing Switzerland 2017 P. Mina-Osorio (ed.), Next-Generation Therapies and Technologies for Immune-Mediated Inflammatory Diseases, Progress in Inflammation Research, DOI 10.1007/978-3-319-42252-7_5
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2 Rationale for Bispecific Biologics in Rheumatoid Arthritis 2.1 M ode of Action of Biologics in RA and Combination Therapies Biologics have greatly improved the treatment and management of rheumatoid arthritis (RA), but there remains a large unmet need. In particular, a minority of patients reach ACR50 let alone ACR70 treatment criteria, and a number of them do not respond at all to therapy. In this respect, it is an attractive thought to combine the effect of multiple modes of action to achieve higher efficacy. Obviously one important aspect here is that the target product profile of the bispecific antibody should be differentiated in comparison to the mere combination therapy. For an indication like RA where chronic dosing for years is likely to remain necessary, availability of a single molecule is likely to remain attractive over co-formulation of two molecular entities for subcutaneous administration. There are also advantages when dealing with just a single molecular entity during clinical development and for manufacturing. Bispecific antibodies where the net effect is higher than the sum of the part, and could not be achieved with a combination of single molecular entities, are certainly
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