1、Journey of a Therapeutic Antibody:From Preclinical to Clinical Proof of ConceptAmanda Woodrooffe,PhDRachel Owen,PhD2Introduction3Overview of Therapeutic Antibodies4Preclinical Target and Biomarker Validation6Table of ContentsEarly Clinical Development 9Authors20Conclusion and References193Introducti

2、onTherapeutic antibodies are on the ascendancy,driven by a significant evolution in antibody engineering and an expanding market.Antibodies have become the fastest-growing class of biologic drugs and are used for treating a wide range of indications,from oncology and immunology to infectious and hem

3、atological diseases.1 Since the first approval in 1986,there are now more than 165 antibody-based drugs,either approved or under regulatory review.In this eBook,we explore the journey of a therapeutic antibody in early development,highlighting the key assays on the critical path from preclinical to

4、clinical proof of concept.Along the way,we also share real-life case studies demonstrating the challenges and opportunities of developing,validating,and implementing robust assays.4Therapeutic antibodies have a broad range of targets,including checkpoint or co-stimulatory markers,cytokines,growth fa

5、ctors,and immune cell markers(see Figure 1).Overview of Therapeutic Antibodies0246CD20HER2CD19EGFRIL-23PD-1SARS-CoV-2TNFVEGFCGRPIL-17IL-6RPD-L1Common antibody targetsNumber of marketed antibodiesThese drugs also come in a variety of configurations,from monoclonal antibodies and multi-specific antibo

6、dies to antibody fragments and antibody-drug conjugates(ADCs)(see Figure 2).Figure 1.Marketed antibodies by targetFigure 2.Variety of therapeutic antibodies and their mechanisms of action35Among the antibodies that have been approved,most are in immunoglobulin G(IgG)format.While antibodies are most