Models were validated using a 10-round cross validation scheme. At each round, 20% of the DEL dataset was held out. This was done using random sampling for the "random" benchmark and using a "Stratified GroupKFold" function from SciKit Learn 48 such that no two compounds in the same cluster were in diderent folds for the OOD set. Clusters were determined using "LeaderPicker" from the SimDivPickers module of RDKit 2023 . The OOD testing splits were further pruned to remove DEL compounds composed of building blocks that were also present in the training set. After cross validation, final models were refit to the entire dataset.