Rare Daily Staff

Synlogic reported positive top-line data from its phase 2 Synpheny-1 study of two experimental therapies— SYNB1934 and SYNB1618—in phenylketonuria, a rare metabolic condition.

The company said following the study of the two experimental therapies it will advance SYNB1934 to a phase 3 registration trial in the first half of 2023.

SYNB1934 and SYNB1618 are orally administered, non-systemically absorbed drug candidates being studied as potential treatments for phenylketonuria (PKU), a genetic disease caused by potentially neurotoxic levels of the amino acid phenylalanine (Phe). Treatment options for PKU are currently limited due to efficacy and safety, and many of those who are treated need additional Phe-lowering. 

Synlogic designed drug candidates to reduce levels of Phe in people with PKU using precision genetic engineering of the well-characterized probiotic E. coli Nissle. SYNB1934 reflects additional optimization to further increase productivity of Phe consumption compared to SYNB1618.

The open label Synpheny-1 enrolled 20 adults with PKU who had a Phe level above 600 μmol/L at screening despite treatment with diet and/or Kuvan. Eleven patients were enrolled in the SYNB1618 arm and 9 were enrolled in the SYNB1934 arm. Ten patients have completed the SYNB1618 arm and 5 patients have completed Arm 2 with SYNB1934.

Both strains demonstrated clinically meaningful reductions in fasting plasma Phe. On an “all comers” basis, the day 14 mean change from baseline in fasting plasma Phe was -20 percent for SYNB1618 and -34 percent for SYNB1934.

Results were consistent and positive across all measured indicators of activity for both drug candidates, including plasma D5-Phe, plasma D5-TCA and urinary D5-HA, with numerically greater changes observed for SYNB1934, consistent with previously shared results in healthy volunteers.

Results from patients who were already taking Kuvan at baseline, and then received SYNB1618 and SYNB1934, were consistent with the overall efficacy profile, demonstrating the potential for adjunctive use.

All adverse events were mild or moderate in severity and were predominantly gastrointestinal (GI) in nature. There were no serious adverse events. Across the study, three patients discontinued due to GI-related adverse events, one withdrew consent, and one patient withdrew following an adverse event of facial flushing that was attributed to a possible allergic reaction.

Full data from the phase 2 study are expected to be presented at upcoming medical meetings and submitted to peer-reviewed medical journals.

“The robust plasma Phe reduction demonstrated by SYNB1934 indicates that it has potential to be a transformative treatment for patients with PKU,” said Aoife Brennan, Synlogic president and CEO.