Synlogic Doses First Subject in Phase 1/2a Trial of SYNB1618 for Treatment of Phenylketonuria
– Second Synthetic Biotic™program to move into clinical
studies in 2018 –
– SAD/MAD study will include healthy volunteers and expansion cohorts of adult patients with PKU –
– Interim data expected in 2018; full data in 2019 –
“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
“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
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.
PKU is caused by a defect in the gene encoding phenylalanine hydroxylase (PAH), a liver enzyme that metabolizes Phe. Phe is an essential amino acid that enters the body as a component of dietary protein and can be toxic if it accumulates in the blood and brain. Current disease management of PKU involves strict dietary protein restriction with the consumption of Phe-free protein supplements. The only currently approved medication, Kuvan®, is indicated for a subgroup of patients and does not eliminate the need for ongoing dietary management. Life-long Phe control is challenging due to the highly restrictive nature of the diet and patients typically experience worsening neurological function depending on the severity of their genetic mutation and their treatment compliance. PKU is diagnosed at birth, and the
About Synthetic Biotic Medicines
Synlogic’s innovative new class of Synthetic Biotic medicines leverages the tools and principles of synthetic biology to genetically engineer probiotic microbes to perform or deliver critical functions missing or damaged due to disease. The company’s two lead programs, SYNB1020 and SYNB1618, target hyperammonemia as a result of liver damage or genetic disease, and phenylketonuria, respectively. Patients with these diseases are unable to break down commonly occurring by-products of digestion that then accumulate to toxic levels and cause serious health consequences. When delivered orally, Synthetic Biotic medicines can act from the gut to compensate for the dysfunctional metabolic pathway and have a systemic effect, with the potential to significantly improve symptoms of disease for affected patients.
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