Drug Discovery, Designing Chemistry and Pharmaceutical Analysis

The dramatic growth of biologics in the past few decades lead to major advances in medical therapy for patients and brought about a shift in the way drug discovery is approached. While biologicals have many diff erent characteristics from small molecule drugs they both share the same concern in that typically only a fraction of the treated population responds favorably, while others may experience lack of effi cacy or even occurrence of Adverse Drug Responses (ADRs). Pharmacogenomic studies for both small molecule therapeutics as well as biologics have shown that diff erent response are oft en explained by host genetic factors, indicating a need for clinical markers for prediction of effi cacy and ADRs. Th e discovery of such genetic biomarkers is challenging, but if successful could lead to competitive advantage for biologicals when they are partnered with their companion diagnostics. Examples of recently identifi ed genetic associations that infl uence response to biologics will be discussed. An improved understanding of host response through careful pharmacogenomics studies can reveal diff erent pathways that impact efficacy and safety of biologicals. This knowledge in turn can help direct eff orts to improve upon the first generation of biologicals by creating molecules with enhanced effi cacy and reduced occurrence of ADRs. Th is field is only beginning to emerge, but with the advances of pathway characterization and use of AI-guided molecular modelling can predicted to impact the next generation of biobetters.