Flow forward: Transforming solid-phase peptide synthesis at Merck

Abstract: Macrocyclic peptides are a growing and promising asset class within the development pipeline at Merck & Co., Inc. For decades, batch-mode solid-phase peptide synthesis (SPPS) has been employed throughout peptide drug discovery and development; however, numerous drawbacks (e.g., high solvent volumes and long processing times) have persisted despite advancements in the technology. To address these limitations, Merck has invested in a novel platform technology, continuous flow solid-phase peptide synthesis (CF-SPPS), to optimize and deliver peptide fragments across reaction scales. Through the identification of key scaling parameters and development of novel variable bed reactors, we have enabled a rapid, data-rich workflow for peptide synthesis that dramatically reduces development efforts, timelines, and waste compared to batch-mode SPPS. Join us as we discuss how our cross-functional team has driven the evolution of CF-SPPS from proof-of-concept to kilo-lab scale.