10144147The Bio Revolution for weight-loss drugs: Enabling biomanufacturing of blockbuster GLP-1 agonistsActiveCollaborative R&DInnovate UKTherapeutic peptides are set to dominate the top-selling drugs list over the next decade. Incretin mimetics such as Semaglutide (brand names Ozempic/Wegovy/Rybelsus) and Tirzepatide (brand names Zepbound/Mounjaro) are projected to make up 5 of the top 10 selling drugs by 2030, with combined sales of $116Bn. Each of these active pharmaceutical ingredients (APIs) incorporates non-canonical amino acids (ncAAs), which are crucial for their therapeutic efficacy, but also prevent their biomanufacturing by conventional recombinant technology. Instead, manufacturers must use chemical synthesis methods with significant challenges for sustainability (due large quantities of harmful solvent waste) and production at scale (due to high capital investment required and rapid growth in demand). Constructive Bio has pioneered an innovative and environmentally friendly method for biomanufacturing therapeutic peptides incorporating ncAAs, leveraging the power of genetic code expansion. This cutting-edge approach involves expanding the repertoire of genetically encoded amino acids to incorporate novel, pharmacologically relevant chemistries. In this project, we will work in collaboration with CPI to develop reagents and production strains for a panel of 5 GLP-1 agonist strains before selecting one for proof-of-concept scale-up to fermentation in 100L tanks with a full product quality benchmarking dataset. This will demonstrate the potential for biomanufacturing methods to replace chemical synthesis methods and pave the way for a more sustainable and scalable peptide manufacturing industry.