BPS 2025
Half-life extension of peptides using fatty acid derivatization; past, present and future opportunities
Søren Østergaard
Senior Principal Scientist, Novo Nordisk A/S
ABSTRACT
Semaglutide and tirzepatide approved for type 2 diabetes and obesity are redefining peptide therapeutics. A molecular engineering technology, fatty acid derivatization, initially applied to insulin, then semaglutide, has now enabled otherwise short-lived peptides to be dosed once weekly and moreover, this technology has unlocked unprecedented efficacy in terms of biological activity. Central to this advancement is the derivatization with a fatty acid, which facilitates the binding of the peptide or protein of interest to albumin (1). Due to the well-defined chemical nature of fatty acids, inherent safety, ease of synthesis and upscale, this technology offers a unique versatile approach to peptide and protein drug discovery.
In this presentation, the focus will be on early and current inventions, illustrating how this technology has been applied to address the challenges in designing long-acting peptide-based therapeutics. Additionally, how these endeavors might pave the way for future advancements in peptide drug design will be discussed.
(1) P. Kurtzhals, S. Østergaard, E. Nishimura, T. Kjeldsen, 2022, Nature Rev. Drug Disc, 22, 59-80, doi.org/10.1038/s41573-022-00529
BIO
Søren Østergaard is a senior principal scientist at Novo Nordisk A/S where he has been working in various peptide projects including peptide synthesis technologies for the last +30 years. He has a long track record of successful peptide drug projects that have resulted in marketed products or compounds in clinical trials. He has been optimizing novel half-life extension methodologies of peptides in order to be able to dose once-weekly or beyond of peptide drugs. Another focus area has been improving the potency/selectivity profile e.g., endogenous peptides or de novo design of dual acting peptides for subcutaneous or oral dosing. In addition, he has also worked with challenges in the bRo5 space, immunogenicity of peptides and proteins (B- and T- cell epitope mapping) and integrating these technologies into the drug discovery process
More than 20 years ago he introduced high throughput array and plate synthesis and have been an early key driver in the implementation of these robotic technologies to successfully speed and improve the peptide drug discovery process at Novo Nordisk.
He is collaborating with academia and has through the years served as supervisor for PhD students. He attends career events representing Novo Nordisk as talent ambassador, giving educational lectures at various courses at Universities in Denmark and Sweden and from time to time invited as PhD assessor. He is the author or co-author of +90 publications and patents.