Oral Therapeutics Platform for Treating Inborn Errors of Amino Acid Metabolism

Project Abstract Syntis Bio is pioneering a groundbreaking approach to treat Homocystinuria (HCU), a metabolic disorder caused by a defect in the cystathionine-β-synthase enzyme, by developing a once-daily oral therapy utilizing a gastrointestinal synthetic epithelial lining (GSEL™) combined with a protease-stable methionine-gamma-lyase (MGL). This innovative strategy aims to effectively manage elevated levels of homocysteine and methionine by enhancing the retention and activity of MGL in the small intestine, thereby addressing both ingested and recirculated methionine without the downsides of current invasive treatments. In this SBIR Fastrack proposal, we propose to optimize an MGL-GSEL formulation (SYNT-202) for robust gastrointestinal adhesion and stability, demonstrate its efficacy in reducing homocysteine levels in mouse models and validate its tolerability and biocompatibility in larger animal models. The goal is to produce a solid dosage form that simplifies administration, ensuring a feasible, long-term disease management strategy for HCU patients and potentially other metabolic disorders, leading to improved dietary flexibility and quality of life.