Synlogic has reported positive interim data from the healthy volunteer (HV) arm of its ongoing Phase l/lla study of SYNB1618 to treat phenylketonuria (PKU) after meeting the trial’s primary objective.
In the first portion of the trial, Synlogic examined SYNB1618 in comparison with placebo (PBO) in single-ascending dose (SAD) and multiple-ascending dose (MAD) cohorts of HVs.
This portion was designed to demonstrate safety and tolerability of SYNB1618 in HVs and to find a suitable dose of the drug for evaluation in patients with PKU.
Results from this portion of the trial are similar to preclinical studies and have shown that oral administration of SYNB1618 led to significant dose-dependent production of biomarkers specifically related to SYNB1618 activity to demonstrate proof-of-mechanism.
Synlogic interim president and CEO and chief medical officer Aoife Brennan said: “The significant dose-dependent production of SYNB1618-specific biomarkers in healthy volunteers is an exciting first step towards delivering a potential therapy for patients with PKU.
“We have identified a dose for the next phase of our ongoing trial in patients with PKU and we look forward to expanding on these interim results when we report top-line data from the patient treatment arm of this trial in mid-2019.
“Importantly, the data also demonstrates the potential for our Synthetic Biotic platform to address conditions in which an engineered living medicine can be designed to perform a specific metabolic function within the gastrointestinal tract.”
The Phase l/lla trial is a randomised, double-blind, PBO-controlled study of orally administered SYNB1618.
It aims to analyse the ascending doses of SYNB1618 administered on a single day, along witth multiple-ascending doses given over a period of seven days.
The trial’s primary objective was to evaluate the safety and tolerability of SYNB1618 in HVs and to indentify an appropriate dose to evaluate in patients with PKU.
Its secondary objectives include characterisation of microbial kinetics of SYNB1618 in feces, as measured by qPCR, and gastrointestinal (GI) tolerability, assessed by GI-related adverse events.
Exploratory goals of the trial were evaluation of pharmacodynamic effects of SYNB1618, including previously identified biomarkers of SYNB1618 activity, tricyclic antidepressant (TCA) level in plasma and HA in urine.