California Institute for Biomedical Research (Calibr) Release: A Novel Peptide Engineering Platform for Generating Stapled Long-acting Peptide Hormones

LA JOLLA, Calif., March 28, 2016 /PRNewswire-USNewswire/ -- A team of researchers at the California Institute for Biomedical Research (Calibr) and The Scripps Research Institute (TSRI) have developed a peptide engineering platform to improve the effectiveness of peptide hormones as treatments for chronic diseases such as diabetes and obesity. As a drug class, peptides offer exquisite specificity and potency, but also present challenges associated with poor stability and short half-life, manifesting in the need for frequent injections, poor patient compliance, and overall compromised efficacy. The results, published today in the Proceedings of the National Academy of Sciences (PNAS) titled "Long-acting Potent GLP-1 Analog Delivered in Microstructure-based Transdermal Patch", described the development of a novel strategy that incorporates a serum protein-binding motif into a covalent side-chain "staple", which rigidifies the bioactive portion of the peptide leading to increased stability and potency.

As a proof-of-concept, this strategy has been successfully applied to generate a highly potent, long-acting glucagon-like peptide-1 receptor (GLP-1R) agonist for the treatment of type 2 diabetes and obesity. Researchers demonstrated that their new GLP-1R agonist, E6, has significantly improved half-life and glucose tolerance following an oral glucose challenge in rodents. Chronic treatment using E6 significantly decreased body weight and fasting blood glucose, improved lipid metabolism, and also reduced hepatic steatosis in diet-induced obese (DIO) mice.

Moreover, the high potency and solubility of E6 permitted the administration of this peptide using MicroCor®, a novel transdermal delivery system developed by Corium International, Inc. In collaboration with scientists at Corium, who co-authored the paper, E6 was successfully formulated in the MicroCor dissolving microstructure transdermal delivery system, and a single five-minute application of the microstructure patch on guinea pigs resulted in bioavailability comparable to subcutaneous injections. Importantly, corresponding improvements in glucose tolerance were sustained for up to four days in guinea pigs following a single application. This delivery approach may offer an effective and patient-friendly alternative to currently marketed GLP-1 injectables and can likely be extended to other peptide hormones. The study exemplifies a robust, modular platform for generating stapled long-acting peptide hormones, and Calibr scientists are now applying this technology to drug candidates for the treatment of other chronic metabolic, cardiovascular, and inflammatory diseases. Calibr is actively seeking strategic partnerships to further develop these molecules for the treatment of unmet medical needs.

Contact:
Weijun Shen
Phone: 858-242-1018
Email: [email protected]

SOURCE The California Institute for Biomedical Research