Director, Peptide Chemistry
A Discovery Case Study: Early Implementation of an Appropriate Screening Funnel is Key to Success for Peptide Therapeutics
A set of important tools to early support peptide discovery studies have been implemented at an early stage so to correctly drive our process of development of peptide therapeutics. In particular in vitro approaches have been set up to identify peptide metabolites, not only in plasma but also in the sub cutaneous tissue, to mimic metabolism at the site of injection that correlates with improved in vivo bioavailability. Peptide drugs are also at risk of raising safety issues, in fact injection, by IV or sc route, can often trigger a non-IgE mediated pseudo allergic reaction. This effect is caused by mast cell activation and consequent histamine release and therefore early implementation of screening of our peptide leads in a human mast cell line is key to dial out potential safety concerns that might become evident only in late development. The aggregation potential and the oligomerization propensities are also very important issues that can impact PK/PD, solubility and immunogenicity. This presentation will cover details of the repertoire of studies that we found to be necessary and indispensable to support our peptide drug discovery efforts.