Synlogic, Inc. (Nasdaq: SYBX), announced that new preclinical data from SYNB1020, a Synthetic Biotic medicine currently being evaluated in an ongoing Phase 1b/2a clinical trial in patients with cirrhosis and elevated ammonia, were presented at Digestive Disease Week (DDW 2018), held June 2-5, 2018 in Washington, D.C. The new preclinical data demonstrate that, in addition to lowering systemic levels of ammonia, administration of SYNB1020 resulted in reduced indicators of liver damage, including liver enzymes and inflammatory markers, fibrosis and gut permeability, providing additional support for the continued development of SYNB1020 as a potential treatment for liver disease.
“Collectively, the preclinical data we have obtained in this model of chronic liver damage demonstrate that, in addition to the dose-dependent blood ammonia-lowering effects that we have previously described, SYNB1020 has additional effects on gut and liver biology that may increase its therapeutic potential as a treatment for liver disease,” said Aoife Brennan, M.B., B.Ch., Synlogic’s interim president and chief executive officer and chief medical officer.
SYNB1020 is a strain of a probiotic bacterium, E.coli Nissle, that has been engineered to convert ammonia (a metabolite that becomes toxic to the body at high levels) into arginine, a beneficial amino acid, making it a potential treatment for diseases, such as cirrhosis, where elevated ammonia is a result of the disease. A phase 1 clinical trial in healthy human volunteers demonstrated SYNB1020 was well-tolerated and provided evidence supporting proof of mechanism. In preclinical animal models of hyperammonemia, orally administered SYNB1020 has been demonstrated to lower blood ammonia in a dose-dependent manner and improve survival in treated animals fed a high protein diet, a major source of ammonia.
In a plenary session at DDW Synlogic presented data demonstrating that oral administration of SYNB1020 in a chronic TAA mouse model:
- Dose dependent reduction in blood ammonia and an increase in blood urea;
- Increased survival;
- Reduced intestinal permeability, a complication of liver disease that can result in leakage of fluid and bacteria from the gut into the bloodstream;
- Ameliorated TAA-induced liver injury demonstrated by reduced release of liver enzymes and hepatic inflammatory cytokines IL-6 and TNF-alpha; and
- Reduced liver fibrosis, as determined by histological staining of liver tissue and lower expression of markers of fibrosis, such as TGF-beta and alpha-SMA.