Predicting effect of novel treatments using molecular pathways and real-world data

In pharmaceutical R&D, predicting the efficacy of a pharmaceutical in treating a particular disease prior to clinical testing or any real-world use has been challenging. In this paper, we propose a flexible and modular machine learning-based approach for predicting the efficacy of an untested pharmaceutical for treating a disease. We train a machine learning model using sets of pharmaceutical-pathway weight impact scores and patient data, which can include patient characteristics and observed clinical outcomes. The resulting model then analyses weighted impact scores of an untested pharmaceutical across human biological molecule-protein pathways to generate a predicted efficacy value. We demonstrate how the method works on a real-world dataset with patient treatments and outcomes, with two different weight impact score algorithms We include methods for evaluating the generalisation performance on unseen treatments, and to characterise conditions under which the approach can be expected to be most predictive. We discuss specific ways in which our approach can be iterated on, making it an initial framework to support future work on predicting the effect of untested drugs, leveraging RWD clinical data and drug embeddings.

Indication Finding: a novel use case for representation learning

Many therapies are effective in treating multiple diseases. We present an approach that leverages methods developed in natural language processing and real-world data to prioritize potential, new indications for a mechanism of action (MoA). We specifically use representation learning to generate embeddings of indications and prioritize them based on their proximity to the indications with the strongest available evidence for the MoA. We demonstrate the successful deployment of our approach for anti-IL-17A using embeddings generated with SPPMI and present an evaluation framework to determine the quality of indication finding results and the derived embeddings.