Synlogic Presents Data from Phase 1/2a Study of SYNB1618 at the Annual Symposium of the Society for the Study of Inborn Errors of Metabolism (SSIEM)
– Advancing clinical development of SYNB1618 as a novel therapy to potentially serve all patients with phenylketonuria –
“Lifetime dietary management of PKU is effective but challenging for patients and there remains a significant unmet need for this population,” said Dr. Vockley, who was a principal investigator on Synlogic’s study. “Physicians, patients and families welcome the development of novel therapies like SYNB1618 that have the potential to impact the lives of all PKU patients.”
The study’s primary objectives were to evaluate safety and tolerability of an early liquid formulation of SYNB1618, as well as clearance of SYNB1618 from the gastrointestinal (GI) tract after cessation of dosing. 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).
“With this study, we have taken another step towards our goal of delivering a safe, oral therapy option for all patients with PKU regardless of age or disease type,” said
Synlogic’s Synthetic Biotic platform leverages the tools and principles of synthetic biology to engineer a non-pathogenic strain of E. coli (Nissle) to perform or deliver specific functions lost or damaged due to disease. SYNB1618, designed to function in the GI tract, has been engineered with two different mechanisms to consume Phe, an essential amino acid that can accumulate to harmful levels in patients with PKU with severe consequences. SYNB1618 is designed to metabolize Phe to harmless compounds including trans-cinnamic acid (TCA) in the blood which is further metabolized in the liver and excreted as hippurate (HA) in the urine. TCA and HA represent specific quantitative biomarkers of SYNB1618 activity as demonstrated by Synlogic’s preclinical data that were published in Nature Biotechnology and in data from healthy volunteers from the first part of this Phase 1/2a study. SYNB1618 is also designed to metabolize Phe to phenylpyruvate (PP) via a second enzyme mechanism, L-amino acid transaminase (LAAD). One of the downstream metabolites of LAAD activity is phenyl-lactic acid (PLA) which can be measured in the urine.
- A statistically significant increase in biomarkers of SYNB1618 activity (TCA and HA) was observed in both healthy volunteers and PKU patients treated with SYNB1618, but not in subjects treated with placebo, indicating that SYNB1618 was able to carry out its designed function and consume Phe in the human GI tract.
- Equivalent biomarker production and tolerability were observed in both patients and healthy volunteers at a dose of 7 x 1010 colony forming units (CFU) supporting the evaluation of a solid oral formulation of SYNB1618 in a bridging study in healthy volunteers to inform dosing in a subsequent efficacy study in patients.
- Evidence of activity in the human GI tract of the second Phe-consuming function engineered into SYNB1618 (LAAD) was provided by data from healthy volunteers.
- There were no treatment-related serious adverse events (SAEs), treatment-emergent AEs were either mild or moderate in severity. Most were GI-related, mild and reversible.
- All subjects cleared the bacteria in the expected time frame. There was no evidence of colonization, and no subject required antibiotics.
- Blood Phe levels were measured in all PKU patients over the course of the study. However, the study was not designed or powered to demonstrate Phe lowering.
In addition to the presentation highlighting results of the Phase 1/2a study of SYNB1618,
SYNB1618 Clinical Development Plans and Upcoming Milestones
About Phenylketonuria (PKU)
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. 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
This press release contains “forward-looking statements” that involve substantial risks and uncertainties for purposes of the safe harbor provided by the Private Securities Litigation Reform Act of 1995, including statements regarding Synlogic’s plans and expectations for the development of SYNB1618. All statements, other than statements of historical facts, included in this press release regarding strategy, future operations, future financial position, future revenue, projected expenses, prospects, plans and objectives of management are forward-looking statements. In addition, when or if used in this press release, the words “may,” “could,” “should,” “anticipate,” “believe,” “estimate,” “expect,” “intend,” “plan,” “predict” and similar expressions and their variants, as they relate to
Caroline Rufo, Ph.D.
Elizabeth Wolffe, Ph.D.