A2A Pharmaceuticals

A2A Pharmaceuticals designs computationally optimized small molecule therapeutics for the treatment of cancer and antibiotic resistant bacterial infections.  Our two oncology programs are focused on inhibiting essential protein-protein interactions in leukemia and in diverse solid tumors. These interactions are critical for cancer progression, but non-essential in normal cells. The antibiotic programs target biosynthetic enzymes in gram-negative bacteria, in pathways not found in humans. The targets selected have no clinically used therapeutics, minimizing susceptibility to resistance; and unlike the numerous follow-on antibiotics currently in development. Our approach integrates interdisciplinary ingenuity with computational tools to design new drug candidates using our proprietary SCULPT platform. Experimentally determined target characteristics guide the selection and placement of fragments to recapitulate key contact points of proteins and/or ligands known to bind. Fragments are incorporated into the target-specific construction of combinatorial in silico libraries, which are designed based on synthetic feasibility. Libraries consisting of thousands to millions of small molecules are iteratively built, and computationally evaluated for potency and optimal ADMET properties. The final selection is made from dozens of iterations, totaling upwards of 100 million compounds.