PEGS Boston 2026 Poster: Accelerating Drug Discovery. De-Risking Complex Multi-specific and Multi-format Biologics with a CMC-Predictive Mammalian Display Platform

Abstract

The development of novel multispecific biologics is hampered by an ‘Innovation-Complexity Paradox’: to efficiently target complex disease, one may need to deploy complex formats. The struggle to turn innovative formats into manufacturable products is a major efficiency bottle neck. Sequential optimization of individual ‘building blocks’ is costly, time-consuming, and high-risk because it is unpredictive of the CMC properties of assembled complex constructs.

We have developed a proprietary, clinically validated Mammalian Display platform that overcomes this flaw by enabling simultaneous multi-parameter optimization in the final format, as demonstrated across symmetric and asymmetric bispecific antibodies. Using precise single-copy gene integration into a defined locus, the platform leverages native mammalian proteostasis pathways as a universal, format-independent quality control sensor. Surface display level correlates directly with developability attributes, such as aggregation propensity. We have observed how this technology powerfully predicts CMC performance across multiple formats.

We demonstrate the power of Mammalian Display with a best-in-class enzyme inhibitor case study, where the platform simultaneously optimized antibody affinity (<15 pM), specificity (>10⁶-fold), and developability for subcutaneous administration, paving the way for the molecule to rapidly progress to phase III clinical trials. This “de-risking by design” approach selects ‘elite’ candidates, enabling the molecule to quickly move from discovery to clinic and solving the core challenges for the next generation of complex therapeutics.