Synlogic Doses First Subject in Phase 1/2a Trial of SYNB1618 for Treatment of Phenylketonuria
Synlogic announced that it has dosed the first subject in its Phase 1/2a clinical trial of SYNB1618. SYNB1618 is a Synthetic Biotic medicine being developed for the treatment of phenylketonuria (PKU), a genetic disorder that results in decreased metabolism and accumulation of the amino acid phenylalanine (Phe), which can lead to seizures and cognitive impairment if not appropriately managed. Patients living with PKU currently have limited treatment options and endure a very restrictive diet that is low in protein, the source of dietary Phe.
“We believe that SYNB1618 has the potential to provide PKU patients with an orally administered therapeutic option to help them maintain their blood Phe levels within the range recommended to prevent long-term complications,” said Aoife Brennan, M.B., B.Ch., Synlogic’s chief medical officer. “Our preclinical studies in mouse models of disease and healthy non-human primates demonstrate that, acting from the gut, SYNB1618 can metabolize Phe from the diet and the blood to lower overall blood Phe. These preclinical studies have provided quantitative biomarkers and have been used to design the Phase 1/2a trial.”
“SYNB1618 is the second Synthetic Biotic medicine to enter clinical studies during the last year. This is a significant milestone for our therapeutic platform and supports our vision of developing a robust pipeline of novel therapeutics,” said JC Gutiérrez-Ramos, Ph.D., Synlogic’s president and chief executive officer. “Applying genetic control and metabolic engineering elements of our proprietary synthetic biology platform to a well characterized single probiotic strain has enabled us to develop Synthetic Biotic medicines with pharmacological potency and predictable biomarkers that allow us to establish dose responses, as well as reproducible manufacturing processes.”
Synlogic’s Synthetic Biotic medicines for the treatment of inborn errors of metabolism, such as PKU, are designed to function in the gastrointestinal tract to convert metabolites that can build up to toxic levels in the blood into harmless metabolites that can be excreted from the body. Elevated Phe levels are toxic to the brain and can have severe consequences. SYNB1618 is designed to consume Phe and convert it into metabolites, including trans-cinnamic acid in the blood which can be further metabolized in the liver and excreted as hippurate in the urine, providing potentially important biomarkers of SYNB1618’s activity.