Synlogic said it opted to discontinue development of SYNB1020 following an interim analysis of Phase Ib/IIa data in 23 patients with cirrhosis and elevated blood ammonia.
Synlogic investors are abandoning ship this morning following a company announcement that it had discontinued development of an early-stage treatment for hyperammonemia, a metabolic disorder characterized by an excess of ammonia in the blood.
Cambridge, Mass.-based Synlogic said it opted to discontinue development of SYNB1020 following an interim analysis of Phase Ib/IIa data in 23 patients with cirrhosis and elevated blood ammonia. While SYNB1020 was well-tolerated in patients with cirrhosis, the company said there was no evidence that ammonia levels in the blood were lowering in patients relative to placebo. Following the announcement, shareholders dumped their stock, plunging prices down more than 30% to $3.37 per share.
Aoife Brennan, president and chief executive officer of Synlogic, said the company was disappointed in the analysis of the early-stage trial. Brennan said the interim-analysis revealed that SYNB1020 did not demonstrate an “activity profile in ammonia lowering that warranted continued development of the program.” Plasma and urinary nitrate increased in subjects treated with SYNB1020, indicating that the strain was active, the company said, but it did not produce the desired effect of lowering ammonia levels in the patients. Detailed results of the Phase 1b/2a study are expected to be presented at a future scientific or medical conference, the company said.
With SYNB1020 now on the scrap heap, Brennan said the company will now focus its resources on SYNB1618 for the treatment of phenylketonuria (PKU), SYNB1891 for the treatment of solid tumors and several new programs in early development.
In July, the company reported positive top-line data from a Phase I/IIa study of SYNB1618. A statistically significant increase in biomarkers of SYNB1618 activity was observed in patients treated with the Synlogic asset but not placebo patients, the company said at the time. PKU is caused by a defect in the gene encoding phenylalanine hydroxylase (PAH), a liver enzyme that metabolizes Phe, an essential amino acid. Phe enters the body as a component of dietary protein and can be toxic if it accumulates in the blood and brain.
In May, Synlogic and Roche teamed up to pair SYNB1891 with Roche’s checkpoint inhibitor Tecentriq (atezolizumab) for the treatment of advanced solid tumors. SYNB1891 is a non-pathogenic strain of the bacterium E. coli that has been engineered to express a Stimulator of Interferon Genes (STING) agonist, which stimulates the innate immune system. At the time of the announcement of the Roche deal, Synlogic said it was expecting to launch a Phase I trial of SYNB1891 in advanced/metastatic solid tumors.
