Benzinga | Oct 28, 2021 07:06AM EDT

Synlogic Announcesd Nature Communications Publication Highlighting Use of Synthetic Biotic Platform to Optimize Therapies for Phenylketonuria

Synlogic, Inc. (NASDAQ:SYBX), a clinical stage company bringing the transformative potential of synthetic biology to medicine, today announced a publication in Nature Communications documenting the engineering of a more potent phenylalanine (Phe)-degrading investigational Synthetic Biotic(tm) medicine for the treatment of phenylketonuria (PKU).

The paper, "Improvement of a synthetic live bacterial therapeutic for phenylketonuria with biosensor-enabled enzyme engineering," illustrates how SYNB1934 was generated through whole cell optimization of the Phe-metabolizing enzyme phenylalanine ammonia lyase (PAL). The process involved a combination of directed evolution and high throughput screening libraries of mutated PAL enzymes. Using this technology over 1 million PAL enzymes were screened and an optimized PAL enzyme was used to engineer SYNB1934. This work was performed through a collaboration between Synlogic and Zymergen. As reported in the paper, using established strain-specific biomarkers of Phe metabolism, in preclinical studies SYNB1934 has shown an approximately two-fold increase in PAL activity compared to SYNB1618, Synlogic's first generation strain for PKU. This two-fold increase in PAL activity has subsequently been confirmed in a Phase 1 study of healthy volunteers.

SYNB1934 is currently being evaluated in the Phase 2 SynPheny-1 study in adult patients with classical PKU, and results are expected in the first half of 2022.

"This research illustrates the capabilities of our team and platform to rapidly generate optimized strains of synthetic biotics for the potential treatment of PKU and other metabolic disorders," said David Hava, Ph.D., Chief Scientific Officer at Synlogic. "The SYNB1934 Phase 1 study produced data highly consistent with our preclinical findings, reinforcing the translational capability of the platform. We look forward to the upcoming results of our Phase 2 patient study of SYNB1934 and the advancement of our PKU program into late stage clinical development."