PEGS Boston 2026 Poster: Antibody Optimization with Broad-Space and Structure-Guided Platforms: Tumbler™ and Targeted Engineering

Summary

Antibodies are increasingly used in drug development due to their ability to target a wide range of antigens. However, many antibody-based drug candidates require additional engineering for optimal therapeutic efficacy in humans. This can include affinity maturation, humanization, pH engineering, enhancement of stability, half life, and other developability parameters. Achieving this broad range of objectives requires a diverse set of technologies and approaches, each tailored to address specific challenges in antibody design and optimization.

Here, we introduce two flexible and complementary approaches to antibody optimization: Tumbler™ and Targeted Engineering. While both rely on rational CDR-focused mutational design for library generation, they differ in their design principles and engineering capabilities. Tumbler enables multi-parameter optimization by exploring a broader sequence space, allowing simultaneous improvement across several molecular attributes, such as affinity maturation, humanization, and induction of cross-binding. In contrast, Targeted Engineering generates libraries tailored to a predefined optimization goal, focusing on obtaining the best possible molecules for specific target characteristics. Both approaches then interrogate their respective libraries with selection pressure to discover optimized clones. Together, Tumbler and Targeted Engineering provide a powerful, unified optimization platform: one that accelerates early multi-parameter improvements and subsequently refines candidates through targeted, goal-specific optimization.