OVERCOMING TECHNICAL CHALLENGES OF BISPECIFIC AND MULTI-SPECIFIC ANTIBODIES USING NOVEL TECHNOLOGY PLATFORMS

BACKGROUND: Bispecific antibodies (bsAbs) and multispecific antibodies (msAbs) are a growing class of next generation biotherapeutics. However, multiple challenges, such as chain mispairing and developability issues are often associated with these complex modalities. METHODS: WuXi Biologics has established bsAb and msAb engineering and development platforms. By replacing CH1/CL domains of one antibody Fab by corresponding T cell receptor (TCR) Cβ/Cα domains, WuXiBody® bsAb technology can ensure the correct heavy-light chain pairing. WuXi Biologics has developed the SDArBody™ platform, which utilizes single domain antibodies (VHH) as building blocks to facilitate the exploration of more complex biologics, such as msAbs. RESULTS: as shown in case studies, the WuXiBody® technology is able to assemble regular mAbs in a ‘plug-and-play’ manner, and that the SDArBody® can be utilized to identify VHH leads and then assemble into msAbs. Both platforms can generate highly functional bsAb and msAb with good developability. CONCLUSIONS: The establishment of WuXiBody® and SDArBody® platforms could greatly meet the needs of biologics developers in pursuit of different biology and therapeutic approaches through bsAbs and msAbs.