734-P: VRB101 Is a Potent Oral GLP-1 Tablet with Once-Weekly Dosing Potential

Introduction and Objective: VRB101 is an oral tablet formulation of ecnoglutide, a cAMP-biased, long-acting GLP-1 analog being developed for the treatment of obesity and type 2 diabetes. VRB101 is formulated with a proprietary permeation enhancer, T2026, with improved oral bioavailability. Phase 1 clinical efficacy, safety and tolerability data were presented previously. Here we present pharmacokinetic (PK) analysis of 30 mg daily dose of VRB101 and the modeled PK data supporting the potential of VRB101 as a once-weekly (QW) oral GLP-1 tablet for the treatment of obesity. Methods: We conducted a randomized, double-blind, placebo-controlled Phase 1 study in healthy adults with and without obesity. Participants were randomized to receive VRB101 escalated to the target doses of 7, 15, or 30 mg QD for up to 6 weeks. PK samples were collected, including up to 7 days after the last daily dose. We used the data to model the PK profile of QW dosing with VRB101. Results: After the last 30 mg daily oral dose of VRB101, PK samples were collected up to 168 hours post-dosing and PK parameters for the 7-day period were calculated. This 7-day PK profile was then used to model the steady state PK of 60 mg, 90 mg and 120 mg QW dosing. The PK model projected 60 mg QW dose to reach a steady state weekly exposure (AUC 0-168h) of 40,500 h*ng/mL, 90 mg QW dose to reach exposure of 58,000 h*ng/mL, and 120 mg QW dose to reach exposure of 77,000 h*ng/mL. These exposures are nearing or exceeding the weekly exposure achieved by 2.4 mg subcutaneous semaglutide or 2.4 mg subcutaneous ecnoglutide. Conclusion: This data supports the rationale for VRB101 to be a QW oral GLP-1 treatment. Compared with subcutaneous injections, oral QW 90 mg and 120 mg VRB101 are projected to match or exceed the weekly exposures of subcutaneous GLP-1 injections. VRB101 is expected to exert potent weight lowering while improving adherence via a more patient-friendly dosing regimen. Once-weekly oral administration represents an opportunity towards more scalable treatment option than currently available injectable GLP-1 receptor agonists. Disclosure M. Fenaux: None. E. Adegbite: Employee; Sciwind Biosciences, Verdiva Biosciences. K. Junaidi: None. W. Guo: Employee; Sciwind Biosciences. J. Deng: None. C.L. Jones: Employee; Sciwind Biosciences, Verdiva Bio. W. Zhong: None. S. Trieu: Advisory Panel; Novo Nordisk. Employee; Verdiva Bio. R. Ho: Employee; Verdiva Bio. Consultant; Beacon Therapeutics, Aiolos Bio. M. Eid: Employee; Verdiva Biosciences, Boehringer-Ingelheim.