Morphic Therapeutic leverages digital chemistry strategy to design a novel small molecule inhibitor of α4β7 integrin

Morphic needed an orally bioavailable small molecule targeting α4β7 integrin for inflammatory bowel diseases (Crohn's, ulcerative colitis), a goal that had eluded the field for over 20 years due to the target's structural similarity to related integrins and the difficulty of balancing potency with oral drug-like properties. Using Schrodinger's LiveDesign for collaborative, remote design cycles, the teams ran over 8,500 FEP+ calculations to improve potency and address pharmacokinetic issues, plus Jaguar for quantum-mechanics-based pKa prediction and membrane permeability modeling. The effort achieved a 1000-fold potency improvement, produced clinical candidate MORF-057 (now in Phase 2b development), and designed compounds with 200x greater potency than AJM, an approved Japanese competitor requiring three daily doses.

Schrödinger is a physics-plus-machine-learning computational platform for molecular design; all top-20 pharma companies by revenue are customers of its drug-discovery software.

This sits in the Build stage of the AI use-case lifecycle: Named examples from the foundation-model labs and platforms pharma teams use to actually construct, train and generate the model or application.