Drug-like antibody design against challenging targets with atomic precision

Computational antibody design has seen rapid progress, with high success rates enabling direct translation to characterization without any high-throughput screening required. In this work, we markedly expand the scope of de novo antibody design by applying our state-of-the-art Chai-2 platform to design drug-like antibodies in full-length monoclonal format. We find that >86% of these full-length mAbs have strong developability profiles on par with therapeutic antibodies. We further show that experimentally determined structures of Chai-2 designs closely match their in silico predictions, demonstrating that Chai-2 produces atomically accurate models of designed antibodies. Building on these foundational capabilities, we showcase two potential applications of Chai-2 against different targets: designing functional antibodies mediating GPCR agonism, and highly specific antibodies selectively binding tumor-specific neoepitopes. Taken together, this work brings new flexibility to modern discovery pipelines, accelerating the path from in silico design to functional validation across both conventional and challenging targets. Beyond reducing the cost and timelines associated with large screening campaigns, in silico design can now open new frontiers for creative, targeted therapeutics that address unmet clinical needs.