Synlogic Posts Positive Interim Data for Synthetic Biotic PKU Treatment

Skeletal structure of Phenylalanine

Skeletal structure of phenylalanine, whose accumulation can cause PKU

Shares of Synlogic, Inc. are climbing this morning after the New York Times highlighted the company’s proprietary synthetic biotics being used to treat patients with phenylketonuria, more commonly referred to as PKU. The same day the article was printed, the company released positive interim data from an ongoing study of its PKU treatment.

PKU is caused by a defect in the gene encoding phenylalanine hydroxylase (PAH), a liver enzyme that metabolizes an essential amino acid known as phenylalanine (Phe). If Phe accumulates in the blood and brain, it can become toxic. Current treatment requires strict dietary control and includes the use of Phe-free protein supplements. It’s estimated there are about 16,500 people living with PKU in the United States.

Cambridge, Mass.-based Synlogic is developing SYNB1618, a synthetic biotic that has been engineered to consume phenylalanine (Phe), an essential amino acid that can accumulate to harmful levels in patients with PKU with severe consequences. SYNB1618 is designed to work in the gastrointestinal tract. This morning, the company released interim data from a Phase I/IIa study with healthy volunteers. The interim data showed the synthetic biotic was both safe and tolerable. The company said that consistent with preclinical studies, the interim data showed that oral dosing of SYNB1618 “resulted in significant dose-dependent production of biomarkers specifically associated with SYNB1618 activity, demonstrating proof-of-mechanism.”

The company’s synthetic biotic platform uses the principles of synthetic biology to “engineer a strain of probiotic bacteria (E. coli Nissle) to perform or deliver specific functions lost or damaged due to disease,” according to company data. SYNB1618 is designed to metabolize Phe to “harmless compounds.” Synlogic said those compounds include 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, therefore, represent specific biomarkers of SYNB1618 activity as demonstrated by Synlogic’s preclinical data, the company said in its announcement.

 “We have identified a dose for the next phase of our ongoing trial in patients with PKU and we look forward to expanding on these interim results when we report top-line data from the patient treatment arm of this trial in mid-2019. Importantly, the data also demonstrate the potential for our Synthetic Biotic platform to address conditions in which an engineered living medicine can be designed to perform a specific metabolic function within the gastrointestinal tract,” Aoife Brennan, Synlogic’s interim president and chief executive officer said in a statement.

Synlogic anticipates topline data from the Phase I/IIa study in mid-2019. The company plans to present final data from this clinical trial at an “appropriate medical meeting.” Additionally, the company said it will continue to “optimize manufacturing process development and formulation of SYNB1618 in preparation for later stage clinical studies.”

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