Synlogic (Nasdaq: SYBX), a clinical-stage company applying synthetic biology to probiotic bacteria to develop novel living medicines, announced that it has dosed the first subject in its Phase 1/2a clinical trial of SYNB1618. SYNB1618 is a Synthetic Biotic medicine being developed for the treatment of phenylketonuria (PKU), a genetic disorder that results in decreased metabolism and accumulation of the amino acid phenylalanine (Phe), which can lead to seizures and cognitive impairment if not appropriately managed. Patients living with PKU currently have limited treatment options and endure a very restrictive diet that is low in protein, the source of dietary Phe.
"We believe that SYNB1618 has the potential to provide PKU patients with an orally administered therapeutic option to help them maintain their blood Phe levels within the range recommended to prevent long-term complications," said Aoife Brennan, M.B., B.Ch., Synlogic’s chief medical officer. "Our preclinical studies in mouse models of disease and healthy non-human primates demonstrate that, acting from the gut, SYNB1618 can metabolize Phe from the diet and the blood to lower overall blood Phe. These preclinical studies have provided quantitative biomarkers and have been used to design the Phase 1/2a trial."
"SYNB1618 is the second Synthetic Biotic medicine to enter clinical studies during the last year. This is a significant milestone for our therapeutic platform and supports our vision of developing a robust pipeline of novel therapeutics," said JC Gutiérrez-Ramos, Ph.D., Synlogic’s president and chief executive officer. "Applying genetic control and metabolic engineering elements of our proprietary synthetic biology platform to a well characterized 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."
Synlogic’s Synthetic Biotic medicines for the treatment of inborn errors of metabolism, such as PKU, are designed to function in the gastrointestinal tract to convert metabolites that can build up to toxic levels in the blood into harmless metabolites that can be excreted from the body. Elevated Phe levels are toxic to the brain and can have severe consequences. SYNB1618 is designed to consume Phe and convert it into metabolites, including trans-cinnamic acid in the blood which can be further metabolized in the liver and excreted as hippurate in the urine, providing potentially important biomarkers of SYNB1618’s activity.
About Synlogic’s Phase 1/2a Trial of SYNB1618 in Healthy Volunteers and Patients with PKU
This clinical trial is a single and multiple dose-escalation, randomized, double-blind, placebo-controlled study of orally administered SYNB1618 in healthy adult volunteers and adult subjects with PKU, designed to evaluate safety, tolerability, kinetics, and pharmacodynamics as well as exploratory end-points associated with the ability of SYNB1618 to metabolize Phe.
The study will evaluate SYNB1618 as follows:
Part 1: A single-ascending dose (SAD) study will be conducted in an inpatient setting over four days in healthy volunteers (HV) who will be evaluated in up to six dose cohorts (3 treated :1 placebo) to identify the maximum tolerated dose (MTD) within the single dose range studied. Up to 24 healthy subjects may be enrolled in this part of the study.
Following attainment of the MTD in HV, a SAD cohort of up to four subjects, previously diagnosed with PKU (≥18 years old with elevated Phe at baseline) will be enrolled and treated (3 treated:1 placebo).
Part 2: A multiple-ascending dose (MAD) study will be conducted in an inpatient setting over 10 days in HV evaluated in up to four cohorts (6 treated:2 placebo) and treated at doses that will not exceed the MTD from the SAD part of the study. This will identify the MTD of SYNB1618 within the multiple-dose range. Up to 32 healthy subjects may be enrolled in this part of the study. Once the highest MAD cohort and the SAD PKU cohort have been completed, a multiple-dose cohort of subjects previously diagnosed with PKU (≥18 years old with elevated Phe at baseline) will be evaluated. Up to 20 subjects with PKU may be enrolled and treated (12 treated:8 placebo) in the MAD PKU cohort.
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