BPS 2025
Reduction in Impurities Formed During Large-Scale Semaglutide Synthesis
John Phipps
VP of Clinical Pipeline Development, CPC Scientific
ABSTRACT
Semaglutide, a member of the GLP-1 class of anti-diabetic drugs, has received widespread attention in recent years due to its development as a treatment for obesity. While the current commercial supply utilizes recombinant DNA manufacturing technology, synthetic methods employing solid phase peptide synthesis (SPPS) and/or convergent peptide synthesis have been developed to produce a generic version of semaglutide. However, the non-enzymatic approach can result in poor product quality and low yields that stymie innovation and development.
To address this, CPC Scientific have designed and used the novel compound Fmoc-Gly-OtBu-FMPB that functions as a linker to AM resin and contains the C-terminal Gly31 required in semaglutide. This innovative approach suppresses formation of impurities, most notably those derived through formation of endo-Gly31-semaglutide. Through use of this novel linker and a convergent fragment-based approach, the purity of semaglutide peptide has been increased to 99.5% when preparing multiple-kilogram batches of the final API.
BIO
John Phipps serves as the Vice President of Clinical Pipeline Development at CPC Scientific, boasting an extensive and distinguished track record in the pharmaceutical sector. His expertise spans biotechnology, chemistry, technology transfer, drug discovery, and protein chemistry, underpinned by a Bachelor of Science in Biochemistry from Colorado State University. John began his career in 1992 as a bench chemist and manager of the Colorado State University core facility from 1999 to 2001, making peptides by SPPS using Boc and Fmoc chemistry. In 2001, John founded Global Peptide Services, serving as president from 2001 to 2008. In 2010, he worked at Bachem as a business development manager until 2017. John joined to CPC Scientific in 2017, and he currently resides in Long Beach, California, and is available to engage peptide and oligonucleotide clients throughout the United States.