Development of a novel peptide-centric sustained release system.
Sheauyu Teddy Hsu Adepthera LLC, 5941 Optical Court, San Jose, CA 95138
Therapeutic proteins and peptides are generally administered parenterally. Due to sensitivity to proteolysis and renal clearance, many peptide therapeutics need continuous administration or frequent doses of injections to achieve efficacy, leading to inconvenience and discomfort to patients. To overcome this obstacle, conjugation or fusion to polyethylene glycol (PEG), fatty acids, albumin, antibodies and unstructured proteins such as XTEN and PAS have been developed to extend the half-life of peptide drug candidates. Among them, pegylation was one of the first modifications shown to extend the circulating half-life by increasing the molecular mass of peptide moiety. Likewise, fusion to Fc, albumin, or other large proteins extends the half-life of peptides by increasing the size of the fusion product. By contrast, lipidation extends the circulating half-life of peptides indirectly through non-covalent interactions with albumin and other serum proteins. These modifications have led to the approval of lipidated GLP-1 (liraglutide), GLP-1R agonist-Fc fusion (dulaglutide) and GLP-1R agonist-albumin fusion (albiglutide). Techniques employing slow-release carriers, including oil suspension, crystal particle suspension, liposomes and biocompatible hydrogels such as PLGA polymers, have also been used to improve the pharmacokinetics, dosage accuracy, patient compliance, and efficacy of peptide therapeutics. However, most of these sustained-release techniques are associated with select disadvantages. For example, the support materials may elicit immunogenic responses, and may not degrade after administration (e.g., PEG and silicone). In addition, these formulations frequently require complex fabrication and manufacturing processes. Therefore, alternative techniques that can further improve the delivery and efficacy of peptide therapeutics are much needed. To improve the development of peptide therapeutics, we have developed a unique peptide-centric formulation that can greatly increase the bioavailability of therapeutics and has a minimum immunogenic footprint. In this presentation, we will discuss the discovery and design of this novel peptide-centric drug delivery system as well as its applications in peptide drug development.
2003-2011 Assistant Professor, Stanford University Department of Obstetrics and Gynecology
2012-Present Managing Director, Adepthera LLC