2631-P: Phase 1 Study and Modelling of a Novel Drug Delivery System for GLP-1RA with Lower Adverse Events and Higher Efficacy

Introduction and Objective: SNA-003 is a sustained-release nanoparticle based injectable formulation with semaglutide as model drug to lower GI adverse event and higher efficacy of GLP-1RA drug. The objective of this pilot study was to characterize the pharmacokinetic properties and safety of SNA-003 in humans relative to a commercially available comparator, Wegovy®, and to simulate multiple PK modelling of SNA-003. Methods: A pilot, open-label, randomized, single-dose, parallel-group study was conducted in healthy adult subjects. Participants received 0.5 or 1.0 mg of SNA-003 or 1.0 mg of Wegovy® as semaglutide dose by subcutaneous route after an overnight fast. Pharmacokinetic parameters including Cmax, AUC0-t, AUC0-inf, Tmax, ke, ka, and t½ were evaluated using non-compartmental analysis. Safety assessments focused on overall adverse events, with particular attention to GI tolerability. Results: Ke and t½were comparable across treatment groups, indicating similar systemic clearance characteristics. SNA-003 demonstrated overall systemic exposure (Cmax and AUC0-t) comparable in magnitude to the Wegovy(R), while exhibiting delayed absorption as reflected by a prolonged Tmax, slower absortion. SNA-003 was well tolerated at both evaluated dose levels. No adverse events were reported in the SNA-003 groups, whereas GI adverse events, including nausea and vomiting, were observed only in the Wegovy® group. Pharmacokinetic modelling also have shown that SNA-003 can achieve 20~30% higher dose with similar adverse event level, and 50% longer duration above Cavg compared with Wevogy®. Conclusion: In this pilot clinical study, SNA-003, a nanoparticle based formulation of GLP-1RA or amylin derivatives, demonstrated promising PK profile with lower adverse events, shorter dose escalation period, higher efficacy caused by higher dosing. Disclosure Y. Park: Employee; Current; SN BioScience.