78-LB: PK Studies in Rats and Minipigs of GB-7001, a Novel Monthly Microsphere Formulation Containing High Drug Content of Semaglutide

Abstract

Semaglutide, a once-weekly GLP-1 receptor agonist, has been developed as a treatment for type 2 diabetes and obesity. Currently, the longest-acting GLP-1 product (including dulaglutide, semaglutide, and tirzepatide) is a weekly injection, and there are no approved once-monthly long-acting injectables. There is a need for a product that lasts up to 1 month to improve patient convenience. GB-7001 is a monthly injectable with high content of semaglutide under development with an improvement that reduces the side effect of existing microspheres. The goal of this study is to investigate the pharmacokinetics (PK) of GB-7001 in rats and minipigs. Pharmacokinetic evaluation in rats and minipigs was performed by a single subcutaneous injection, and semaglutide concentration in serum was analyzed by liquid chromatography-tandem mass spectrometry. GB-7001 had a spherical shape with a D50 value of 34.4 µm. The drug content of semaglutide was determined to be 18.0%. Regardless of the high drug content, the sustained release of GB-7001 was shown for up to 28 days without an initial burst and without a lag phase. Although the release rate of GB-7001 slows after 28 days, semaglutide was detected within the quantifiable range for up to 56 days. In conclusion, GB-7001 is an improved 1-month semaglutide injectable that has shown promising results in PK studies in rats and minipigs. Further preclinical studies of the final formulation are scheduled, and GB-7001 is planned to apply for IND once the final formulation is selected. Disclosure E. Seol: None. Y. Kim: None. Funding Ministry of Health & Welfare, Republic of Korea (HI21C1732)