Peptides possess enormous potential to contribute to the current standard of care across many therapeutic areas. By virtue of their inherently short plasma residence time, it is advantageous to identify robust strategies to extend their time-of-action in circulation to lessen the burden of frequent injections. GIP/GLP-1-based dual agonists represent a novel approach to treat diabetes, but such peptides still require protraction in circulation to reduce the burden of frequent injections. In this study, a GIP/GLP-1-based dual-agonist peptide was derivatized with iodoacetamide and conjugated to thiol-bearing time-extension moieties. Four different time-extension technologies were evaluated and compared: native human albumin, XTEN (3 sizes), heparosan (3 sizes), and hydroxyl ethyl starch (3 sizes). The presentation will discuss the in vitro activity of the peptide analogs against the GLP1-R and GIP-R, as well as their pharmacokinetic and pharmacodynamic characteristics in preclinical in vivo models.
Adam Mezo, PhD. is currently a Sr. Research Advisor and leads a team of discovery peptide and protein chemists at Eli Lilly and Company in search of next-generation therapeutics primarily in the fields of endocrinology and neurology. Prior to this role, he spent 12 years at Biogen Idec and Syntonix Pharmaceuticals in a variety of roles, most recently as a Director, Molecular Discovery, where he led a diverse team of chemists, biochemists, and molecular biologists in the discovery and development of peptide and protein therapeutics in the fields of hemophilia and immunology. He performed postdoctoral work at the Massachusetts Institute of Technology in the field of peptide chemistry, received a Ph.D. in organic chemistry from the University of British Columbia in 1999 and a B.S. from Queen’s University (Kingston, Canada) in 1993.