754-P: Development of a Novel One-Month Long-Acting Injectable Semaglutide (IVL3021) and Tirzepatide (IVL3024) with Well-Controlled Pharmacokinetic Profiles and Enhanced Quality of Life Window

Introduction and Objective: Microsphere-based long-acting injectables (LAIs) have been used to replace frequent treatments with extended therapies. The core technology in LAIs lies in controlling release profiles to enhance compliance, effectiveness, and safety by reducing bursts and maintaining therapeutic drug concentration. This study focuses on semaglutide (Sema), a GLP-1 receptor agonist for diabetes and obesity. Despite its effectiveness, Sema is associated with gastrointestinal AEs, a common issue for GLP-1 agonist users. Other LAIs also face challenges, such as fluctuations in plasma drug levels leading to GI troubles. These underscore the need for a stable, controlled delivery system. Encapsulating Sema into microparticles for controlled release is challenging due to its unique characteristics but is essential for improving quality of life (QOL) and outcomes. Methods: We present IVL3021, a one-month LAI of Sema developed with IVL-DrugFluidics® technology. Its morphology was examined via SEM, and size distribution was analyzed using PSA. Encapsulation efficiency (EE%) was determined by HPLC. Non-clinical studies in minipigs and rats evaluated pharmacokinetic (PK) profiles and optimized the formulation. Human PK predictions using non-clinical data determined an appropriate clinical dose. Results: IVL3021 exhibits smooth, uniform morphology with high encapsulation efficiency (>97.0%). Preclinical studies showed IVL3021 sustains plasma Sema concentrations for 4 weeks without burst release. Human PK simulations demonstrated stable plasma exposure, minimizing GI AEs and providing consistent therapeutic effects. Another GLP-1 receptor-targeting drug, tirzepatide LAI, is also under development. Conclusion: In conclusion, IVL3021 shows promis as a one-month LAI for managing obesity and diabetes. Further preclinical evaluations are underway. Disclosure J. Kim: None.