Today, we expand zero-shot drug design beyond binding to the design of multifunctional medicines, the intracellular proteome, and state-of-the-art atomic precision with our model, JAM-2. In a new report (below), we show: 1. The first drug-grade, fully computationally designed multispecific antibodies against five peptide-MHCs: Routine picomolar T-cell activation/cell-killing EC50s, >100-fold selectivity, and drug-like developability 2. The first fully generatively designed, drug-grade dual-variant KRAS G12 multispecifics: They recruit primary T-cells from human donors to kill G12V and G12C presenting cells at pM to single-digit-nM potency, completely sparing wild-type. 3. Atomic accuracy, from sequence alone: Angstrom-level agreement between Cryo-EM and JAM-2 de novo designs, requiring only target sequences (not structure) as input. 4. Unrivaled speed with an AI-native in-house wet lab: Designed, built, and tested five programs in one parallelized campaign, end-to-end in-house in ~6 weeks. 5. A higher validation bar for AI-generated drug candidates: In a field increasingly rife with hype and uneven standards of proof, we provide the highest quality public wet-lab validation of AI-designed antibodies to date. We share experimental methods in full, and invite folks to adopt and build on these standards. Truly individualized therapies will be the most important contribution of AI in drug design. These advances help accelerate this future.
