Synlogic Presents Preclinical Data from Synthetic BioticTM Medicine, SYNB1618, for the Treatment of Phenylketonuria
– Data presented in plenary session at ASM Microbe 2018 demonstrate lowering of blood phenylalanine (Phe) levels in an animal model of PKU and non-human primates (NHPs) –
“For patients with PKU, life-long disease management can be challenging due to the protein-restricted diet required to accompany currently available treatments. We are encouraged by the preclinical data presented at ASM Microbe, which support the development of orally administered SYNB1618 as a potentially broadly applicable therapeutic option for patients,” said Aoife Brennan, M.B., B.Ch., Synlogic’s interim president and chief executive officer and chief medical officer. “We are currently exploring production of these same biomarkers in an ongoing Phase 1/2a clinical trial in healthy volunteers and patients with PKU, and look forward to reporting interim safety data from the dose-escalation portion of this trial in the second half of 2018.”
Synlogic’s Synthetic Biotic medicines for the treatment of inborn errors of metabolism, such as PKU, are designed to function in the gastrointestinal (GI) tract to convert metabolites that can build up to toxic levels in the blood into harmless metabolites that can be excreted from the body. SYNB1618 is a strain of a probiotic bacterium, E.coli Nissle, that has been engineered to metabolize Phe, an essential amino acid that at high blood levels can lead to cognitive damage, into harmless compounds, including trans-cinnamic acid (TCA). TCA can be further metabolized in the liver and excreted as hippurate in the urine, suggesting TCA and hippurate are potentially quantitative biomarkers of SYNB1618 activity.
In a Plenary Session at ASM Microbe, “Precision Microbiology,” Synlogic scientist, Vincent Isabella, Ph.D., presented data, demonstrating that:
- Phe is abundant in the small intestine and is derived from two sources, the diet and the blood. Phe in the blood re-enters the GI tract in the form of enzymes and secretions via a process known as enterorecirculation; and
- In a mouse model of PKU and in healthy NHPs, orally administered SYNB1618 can result in significant decreases in blood Phe levels and dose-responsive pharmacokinetics, as determined by dose-dependent production of biomarkers, such as plasma TCA and urinary hippurate.
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 National PKU Alliance estimates that there are currently 16,500 people living with the disorder in the U.S.
Synlogic is pioneering the development of a novel class of living medicines, Synthetic Biotic medicines, based on its proprietary drug development platform. Synlogic 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 PKU, respectively. 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. In addition, the company is leveraging the broad potential of its platform to create Synthetic Biotic medicines for the treatment of more common diseases, including liver disease, inflammatory and immune disorders, and cancer. Synlogic is collaborating with AbbVie to develop Synthetic Biotic-based treatments for inflammatory bowel disease (IBD). For more information, please visit www.synlogictx.com.
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Source: Synlogic, Inc.