Novel Therapeutic Modalities Target the Undruggable

- Novel Therapeutic Modalities Target the Undruggable Absci’s Origin-1 uses generative AI to design *de novo* antibodies for “zero-prior” epitopes, achieving nanomolar affinity for IL36RA in squamous cell carcinomas. It’s a solid step toward rational antibody design, bypassing labor-intensive screens. Meanwhile, Expedition Medicines applies AI to covalent small molecules, targeting shallow pockets on undruggable regulators. They train on high-throughput mass spec data, not noisy DNA-encoded libraries, aiming for clinical proof points with Pfizer. 1910 Genetics tackles macrocyclic peptides with PEGASUS, balancing oral convenience with biologic specificity. Their CANDID-CNS model predicts blood-brain barrier penetration with 87% accuracy, outperforming industry standards. Strand Therapeutics offers programmable mRNA as an “encrypted message,” using microRNA sensors to restrict expression to tumor cells, avoiding off-target effects. STX-001 showed an abscopal response in Phase I. These tools expand the druggable genome, one algorithm at a time.