A Sophisticated Technology Platform Enabling Rapid & Sustainable Scale-Up Of GLP-1 Analogs

Dominik Sarma, Senior Market Manager, Gyros Protein Technologies, aimed to uncover the role of peptide synthesis within the field of obesity treatment. He highlighted how Gyros’ advanced technology platform can be used to manufacture GLP-1 analogues and other complex molecules. Sarma suggested that the key advantage of the platform is its ability to scale up rapidly and sustainably. Sarma stressed that GLP-1 analogues are not a major challenge themselves but also represent common synthesis challenges for peptide synthesis: they accumulate many impurities, making the downstream process more complicated. Additionally, he said: “They're (GLP-1 analogues) often prone to aggregation and gelation, which requires certain knowledge and expertise and handling up and downstream.” Furthermore, pegylations, conjugations to proteins, and other modifications can make it complicated to convert a hit into a decisive lead. So, the main challenge is that a lot of synthesis throughput is required to get all the hits tested.  They become more complex, with modifications and complexity leading to a request for higher purity. Alongside this, Sarma mentioned the importance of scaling up in a green manner. HPLC represents 90 – 95% of the purifications being done for peptide purification, meaning it isn’t the capability of HPLC that poses a challenge. Instead, Sarma suggests that the distinct nature of the technology presents an issue. He elaborated further on this, explaining that one needs both synthesis infrastructure and purification infrastructure for HLPC and there is a process handover i.e. an extra step. The presentation introduces Belinda, a virtual peptides full-stack scientist, who encounters problems with throughput, complexity, and purity during the peptide synthesis process. Sarma discussed the catch and release purification method, which seamlessly integrates into the synthesis workflow and empowers synthesis scientists to perform part of the purification.  Thus, reducing the burden on HPLC and improving efficiency. To back this, Sarma provided examples, such as the synthesis of liraglutide and semaglutide, demonstrating the effectiveness of the catch and release method in achieving high purity and yield. His team investigated two approaches: direct synthesis with a building block, a late-stage modification on PEC, and late-stage modification on the solid phase peptide synthesis resin. The direct synthesis approach achieved 93% purity with a good recovery rate. The late-stage modification on PEC and SPPS resin also showed promising results, with the PEC method providing a high purity and yield. Gyros Protein Technologies also teamed up with Pplus Medical to develop a sophisticated collagen-related peptide using the PEC technology. To sum up, the catch and release purification method offers benefits such as higher capacity, reduced solvent usage, and the ability to scale up using existing infrastructure. These features make it a valuable tool in peptide drug development.