Synlogic has dosed the first subject in its Phase I/IIa clinical trial of SYNB1618, a Synthetic Biotic medicine being developed to treat phenylketonuria (PKU).
PKU is a genetic disorder that leads to decreased metabolism and accumulation of the amino acid phenylalanine (Phe), which can cause seizures and cognitive impairment if not properly managed.
Under the single and multiple dose-escalation trial, SYNB1618 will be orally administered to healthy adult subjects.
The trial is also designed to investigate safety, tolerability, kinetics, and pharmacodynamics, as well as exploratory end-points associated with the ability of SYNB1618 to metabolise Phe.
In the first part of the trial, Synlogic will carry out a single-ascending dose (SAD) study in an inpatient setting over four days in healthy subjects who will be evaluated in up to six dose cohorts to identify the maximum tolerated dose (MTD) within the single dose range studied.
It aims to enrol up to 24 healthy subjects.
After achieving MTD, the trial will enrol and treat a SAD cohort of up to four subjects, previously diagnosed with PKU.
The second part of the trial will involve a multiple-ascending dose (MAD) study that will be conducted in an inpatient setting over ten days. The subjects evaluated will be in up to four cohorts, treated at doses that will not exceed the MTD from the SAD part of the study.
Up to 32 healthy subjects are expected to be enrolled in this part of the trial, which aims to determine the MTD of SYNB1618 within the multiple-dose range.
Following the completion of the highest MAD cohort and the SAD PKU cohort, the trial will analyse a multiple-dose cohort of subjects previously diagnosed with PKU.
The MAD PKU cohort of the study plans to enrol up to 20 patients with PKU.
“SYNB1618 is the second Synthetic Biotic medicine to enter clinical studies during the last year,” Synlogic president Dr JC Gutiérrez-Ramos said.
“This is a significant milestone for our therapeutic platform and supports our vision of developing a robust pipeline of novel therapeutics,
“Applying genetic control and metabolic engineering elements of our proprietary synthetic biology platform to a well-characterised single probiotic strain has enabled us to develop Synthetic Biotic medicines with pharmacological potency and predictable biomarkers that allow us to establish dose responses, as well as reproducible manufacturing processes.”