Accelerating Early Phase Development through Efficient Implementation of Molecular Design and Platform Knowledge

Efficient progression of a diverse BioPharm Portfolio from Target through to FTIH requires the development organization to effectively leverage platform technologies, employ phase appropriate CMC development and characterization, and rely on risk based allocation of resources. This presentation will illustrate GlaxoSmithKline’s strategy for integrating molecular design with standardized technology platforms in early phase CMC to enable accelerated delivery of FTIH assets. Our embedded Molecular Design Intent (MDI) process aims to marry in silico screening with appropriately tiered supporting wet-work (i.e., biophysical screening, physiochemical screening, and pre-formulation studies) to insure desirable patient safety and drug efficacy is built into every final candidate selected molecule. It enables key CMC risks to be identified and compatibility with established process, analytical and formulation platforms to be assessed. The resulting knowledge is used to help prospectively define the scope of development required for subsequent progression into Tox and CTM production. Key quality parameters for all candidate selected molecules are monitored on an ongoing basis including target engagement and understanding of MOA, serum characteristics, sequence and heterogeneity, stability and solubility, and early development yields. This differential development approach has helped significantly reduce overall cycle times and increased throughput of commercializable BioPharm candidates in our portfolio.