Engineering multispecific antibodies with complete killing selectivity through the closed-loop integration of machine learning and high-throughput experimentation.

Justin Grace¹, Pierre-Yves Colin¹, Dan Foxler¹, Winston Haynes¹, Catherine Howsham¹, Leo Kassimatis¹, Lida Mavrogonatou¹, Rebecca Mighell¹, James McClory¹, Michael Mullin¹, Tom Ogola¹, Alex Townsend¹, Sujata Ravi¹, Leo Wossnig¹, Gino van Heeke¹

¹LabGenius Therapeutics, R&D, London, UK.

PubMed PMC DOI PDF

Abstract

On-target, off-tumor toxicities remain a major barrier for T-cell engagers in solid tumors. We present EVATM, a closed-loop design platform integrating high-throughput functional assays with multi-objective Bayesian optimization to explore combinatorial T-cell engager (TCE) spaces. In a HER2×CD3 case study, iterative design-build-test-learn cycles traversed 44,160 designs defined by valency, topo…

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