138-LB: First-in-Human Study of YG1699, an SGLT1 and SGLT2 Dual Transporter Inhibitor

YG1699 is an orally-delivered, small molecule drug candidate that inhibits both the sodium glucose transporter 1 (SGLT1, IC50 = 16.6 nM) and the sodium glucose transorter 2 (SGLT2, IC50 = 1.49 nM). In the preclinical studies, YG1699 could suppress plasma glucose increases following acute glucose challenges in rat oral glucose tolerance tests, and decrease plasma glucose levels in db/db mice in a dose dependent manner. YG1699 can suppress intestinal glucose absorbance and increase both urine and fecal glucose excretion. In addition, YG1699 could significantly increase plasma GLP-1 and PYY levels in animal models. In this upcoming conference, we would like to report our first-in-human clinical trial for YG1699. This clinical study was conducted in USA (Identifier: NCT03953092) with 64 healthy volunteers participated in this single ascending dose (SAD) and multiple ascending dose (MAD) as well as food effect studies. In this Phase 1 clinical trial, YG1699 was well tolerated at all dose levels and produced a dose-dependent increase in urinary glucose excretion in both SAD and MAD studies. YG1699 also demonstrated a very good pharmacokinetic profile with linear, and dose-dependent exposure. The data also show that YG1699 has adequate half-life that can support once daily dosing in Phase II clinical trials. Adverse events were low and generally mild and no SAEs were observed.