Development of an Oral Methionine-Gamma-Lyase Enzyme for the Treatment of Homocystinuria

Abstract - Development of an Oral Methionine-Gamma-Lyase Enzyme for the Treatment of Homocystinuria Syntis Bio is developing Syn-202, a novel methionine gamma-lyase (MGL) enzyme therapy aimed at correcting the metabolic dysregulation in Homocystinuria (HCU), a rare pediatric disorder caused by mutations in the cystathionine-β-synthase (CBS) enzyme. This genetic defect leads to the toxic accumulation of methionine and homocysteine, disrupting critical metabolic pathways and resulting in severe neurological symptoms, developmental impairments, and life-threatening metabolic crises. Current treatments, which primarily rely on dietary methionine restriction, are challenging for young children and patients in resource-limited settings to adhere to, leading to poor compliance and poor outcomes. Syn- 202 offers a more effective and patient-friendly alternative by enzymatically replicating the effects of dietary methionine restriction in a convenient oral formulation. Additionally, Syn- 202 is engineered for proteolytic and pH stability, overcoming the delivery challenges that often limit the efficacy of oral biologics, ensuring consistent and reliable activity.