Optimization of Peptide Drug Exposures for Pharmacological Efficacy: DMPK Considerations

Peptide drugs have the potential to expand the druggable proteome but have historically suffered from challenges limiting optimal exposures near the target site. We describe these longstanding challenges, and present techniques that can be utilized to reliably assess metabolic stability and cellular permeability for peptide drugs targeting intracellular proteins. Factors driving pharmacological efficacy will be discussed, in addition to the approaches aimed towards improvement of systemic and target-adjacent exposures for peptide therapeutics, thereby paving the road to enable therapeutic application for this novel modality.