Developability considerations for bispecific and multispecific antibodies

Area of Science:

• Biotechnology and Pharmaceutical Sciences
• Immunology and Molecular Biology

Background:

• Bispecific antibodies (bsAb) and multispecific antibodies (msAb) offer novel therapeutic strategies by targeting multiple epitopes simultaneously.
• These advanced biologics hold promise for treating challenging and previously incurable diseases.
• Effective development necessitates rigorous assessment of antibody developability early in the pipeline.

Purpose of the Study:

• To summarize critical aspects of developability assessment for bispecific and multispecific antibodies.
• To provide guidance for creating comprehensive developability assessment plans tailored to specific bsAb/msAb formats.
• To facilitate the selection of promising antibody candidates for further development.

Main Methods:

• Review of established and emerging methods for assessing protein-based therapeutic developability.
• Identification of key developability considerations specific to bsAbs/msAbs, including format, immunogenicity, specificity, stability, and production.
• Development of a strategic framework for comprehensive developability assessment.

Main Results:

• Current methods for developability assessment are often not validated for complex bsAbs/msAbs.
• Key factors influencing bsAb/msAb developability include molecular format, immunogenicity, specificity, stability, and scalability of production.
• A structured approach is crucial for evaluating the potential of these advanced therapeutic modalities.

Conclusions:

• Early and thorough developability assessment is essential for advancing bispecific and multispecific antibodies.
• A tailored, robust assessment plan is required to address the unique challenges of bsAb/msAb development.
• This strategic approach supports the successful progression of promising antibody candidates towards clinical application.