Synlogic, Inc. announced the publication in Science Translational Medicine of clinical data from its Phase 1 clinical study in healthy volunteers and supporting preclinical data from its investigational Synthetic Biotic candidate, SYNB1020. The data support the continued development of SYNB1020 which is currently being evaluated in a Phase 1b/2a clinical trial in patients with cirrhosis and elevated blood ammonia. Long-standing evidence supports the importance of the gastro-intestinal (GI) tract as the major source of ammonia in the systemic circulation. The current standard-of-care for conditions that result in hyperammonemia, including hepatic encephalopathy stemming from liver damage and urea cycle disorders (UCDs), which are genetic diseases, employ orally administered approaches such as antibiotics, laxatives and ammonia scavengers. However, each of these agents has limitations resulting in a need for additional therapies to manage hyperammonemia. Synlogic’s Synthetic Biotic platform leverages the tools and principles of synthetic biology to engineer a strain of non-pathogenic bacteria (E. coli Nissle) to perform or deliver specific functions lost or damaged due to disease. Orally administered SYNB1020 has been designed to respond to the low oxygen environment of the large intestine to convert ammonia into arginine, an amino acid. In addition, Synthetic Biotic medicines are engineered to limit their replication after manufacturing so that they do not grow or colonize the GI tract. The preclinical data demonstrate that orally administered SYNB1020 is well tolerated in mice and NHPs, clears rapidly from the GI tract following completion of dosing and is not found in tissues outside the GI tract. When OTC spfash mice, a model of a urea cycle disorder (UCD), were fed a high protein diet to increase their blood ammonia levels, those that were orally dosed with SYNB1020 demonstrated lower blood ammonia and increased survival compared to mice that received heat-killed, inactive SYNB1020. Similar data were obtained in a mouse model of liver damage (TAA model). The clinical data from Synlogic’s Phase 1 clinical study demonstrate that in healthy volunteers, orally administered SYNB1020 was safe, well tolerated, at daily doses up to 1.5 x1012 colony forming units, and cleared from the gastrointestinal tract within two weeks. In addition, dose-dependent elevation in plasma and urine of nitrate, a biomarker of SYNB1020 activity, was observed in healthy volunteers treated with SYNB1020 but not in those treated with placebo, demonstrating proof of mechanism. Synlogic is currently evaluating SYNB1020 in a Phase 1b/2a clinical trial in patients with cirrhosis and elevated blood ammonia for the management of systemic ammonia levels and expects to report data in mid-2019.