A Monthly Amylin and GLP-1 Agonists Combination Injectable Enabled by Novel Single-Process Biodegradable Microsphere Manufacturing

Introduction and Objective: Cagrilintide is a long-acting amylin analog developed for obesity and metabolic diseases. Combination therapy with GLP-1 receptor agonists, including semaglutide, has demonstrated enhanced weight reduction through complementary mechanisms compared with GLP-1 monotherapy. Current development strategies rely on weekly administration of each component, typically requiring separate storage and injection. While a once-monthly, long-acting co-formulation could reduce injection burden, improve adherence, and enhance treatment convenience, co-formulation presents physicochemical instability risks including aggregation or precipitation. Methods: Long-acting Cagri-Sema Injectables were prepared using biodegradable polymers via an emulsion-based microsphere fabrication process. A single-process manufacturing approach was applied to enable simultaneous incorporation of both Cagri-Sema within one production workflow. The pharmacokinetics of Cagri-Sema were evaluated in rats, and plasma concentrations of cagrilintide and semaglutide were maintained for more than 28 days. Results: Both cagrilintide and semaglutide remained stable when incorporated through the single-process manufacturing approach, with no excessive initial burst release. Stability was also maintained in both co-encapsulated and individually encapsulated microspheres supporting feasibility of combination monthly administration. In rat PK studies of Cagri-Sema microspheres after a single injection, plasma cagrilintide and semaglutide concentration was kept more than 28 days. Conclusion: The biodegradable microsphere platform enables once-monthly, combination of Cagri-Sema through a single-process manufacturing approach. By reducing injection frequency from weekly dual administration to monthly injection, this strategy may improve treatment convenience and adherence in long-acting combination therapy development for obesity and metabolic disease. Disclosure: J. Lee: None. B. Kim: None. E. Seol: None. H. Lee: None.