Senior Project Manager, Immunoinformatics EpiVax Inc Providence, Rhode Island
The What-if Machine (WhIM) is an iterative algorithm that models (in silico) nearly all impurities that may occur due known failures in the peptide manufacturing process, such as amino acid deletions, insertions and side chain modifications. WhIM generates a comprehensive list of hundreds of thousands to millions of theoretical impurities, depending on sequence length. All of the generated impurity sequences are scored and ranked with well-established immunoinformatics tools, EpiMatrix and JanusMatrix, at both an overall and a neo-epitope restricted level. EpiMatrix predicts T cell epitope content while JanusMatrix assesses the putative T cell epitopes for potential human homology-induced tolerance. A calibrated risk profile for the novel or generic peptide drug and its WhIM-generated ranked list of potential impurities is produced. Here we will show WhIM analysis examples for two generic peptide drugs (Salmon Calcitonin and Teriparatide) and the in vitro validation of WhIM-identified high-risk Teriparatide impurities.
learn about WhIM, a novel in silico tool for prediction of peptide impurities
understand the types of impurities that can result from synthetic peptide manufacturing
understand the benefit of in silico immunogenicity assessment during the early phase of drug development.