Synlogic, Inc., (Nasdaq: SYBX), a clinical stage company developing a novel class of Synthetic BioticTM therapeutics, announced positive top-line clinical data from patient cohorts of a randomized, double-blind, placebo-controlled Phase 1/2a study of SYNB1618, which is being developed for the treatment of phenylketonuria (PKU). The study’s primary objectives were to evaluate safety and tolerability of an early liquid formulation. Exploratory outcomes were related to the assessment of the pharmacodynamic effects of SYNB1618, including measurement of previously identified biomarkers related to SYNB1618’s engineered ability to consume phenylalanine (Phe).
A statistically significant increase in biomarkers of SYNB1618 activity was observed in SYNB1618-treated subjects but not in those treated with placebo. The full data set from the Phase 1/2a study will be discussed in an oral presentation at the upcoming annual symposium of the Society for the Study of Inborn Errors of Metabolism (SSIEM) to be held in Rotterdam, September 3-6, 2019.
“These data in PKU patients demonstrate that SYNB1618 was well-tolerated by patients and provide a clear path forward for the program. Together with the biomarker data from the healthy volunteer cohorts, we have built a dose-response model that demonstrates SYNB1618’s potential to achieve clinically meaningful reduction of blood phenylalanine levels in patients with PKU”
said Aoife Brennan, M.B., B.Ch., Synlogic’s president and chief executive officer.
“This important milestone demonstrates the potential of our Synthetic Biotic development platform in patients and brings us a step closer to our goal of treating all PKU patients, regardless of age or disease type.”
SYNB1618 Clinical Development Plans and Upcoming Milestones
Synlogic has regulatory alignment for plans to initiate a randomized, double-blind, placebo controlled bridging study of a new solid oral formulation of SYNB1618 in healthy volunteers. In this bridging study, Synlogic plans to select optimal doses of SYNB1618 for an efficacy study in patients with PKU designed to evaluate blood Phe-lowering. Synlogic has developed a robust and reproducible process and manufactured a new solid formulation of SYNB1618 that maintains strain viability and activity. The solid oral formulation with improved quality attributes may enable dosing to higher activity. In addition, the convenience of a solid SYNB1618 formulation enables a larger out-patient efficacy study in patients. Synlogic expects to initiate the SYNB1618 efficacy study in the first half of 2020.
About the Phase 1/2a Trial Design
Synlogic’s Phase 1/2a trial was a randomized, double-blind, placebo-controlled study of an orally administered early liquid formulation of SYNB1618. The study had two parts; the first evaluated ascending doses of SYNB1618 or placebo administered on a single day and multiple ascending doses administered over seven days in healthy volunteers (HV). The second part evaluated SYNB1618 as a single dose and as multiple doses in patients with PKU. The study’s primary objectives were to evaluate safety and tolerability of SYNB1618. Exploratory endpoints assessed the pharmacodynamic effects of SYNB1618, including measurement of biomarkers related to SYNB1618’s engineered ability to consume Phe. The Phase 1/2a study was not designed or powered to measure Phe-lowering in SYNB1618-treated subjects.
The results of the HV part of this study were reported in September 2018. These data demonstrated that SYNB1618 was safe and established a dose that was well-tolerated for evaluation in patients with PKU. The secondary objective was to characterize the microbial kinetics of SYNB1618 in feces, as measured by qPCR. Exploratory outcomes were related to the assessment of the pharmacodynamic effects of SYNB1618, including measurement of biomarkers related to SYNB1618 activity and, importantly, confirming that both pathways engineered to consume Phe are operational within the human GI tract.