Synlogic Presents Data Demonstrating Reductions in Plasma Phenylalanine Levels in Patients With Phenylketonuria Treated With SYNB1618

Synlogic, Inc. recently announced presentation of interim data from the company’s Phase 2 SynPheny-1 clinical trial showing that treatment with the investigational Synthetic Biotic medicine SYNB1618 resulted in significant reductions in plasma phenylalanine (Phe) levels in patients with phenylketonuria (PKU). Results were presented by Dr. Jerry Vockley, MD, PhD, in a late-breaking oral presentation during the International Congress of Inborn Errors of Metabolism Meeting in Sydney, Australia.

In an interim analysis of eight patients, treatment with SYNB1618 was associated with a 40% reduction in D5-Phe absorption after a meal challenge, a 20% reduction in mean fasting plasma Phe across all subjects, and a >250 µM mean reduction in fasting plasma Phe among responder subjects. Treatment with SYNB1618 was also generally well tolerated, with no serious adverse events and a tolerability profile consistent with results from previous Phase 1 studies.

“PKU remains a devastating disease on multiple dimensions. Despite approved medicines, many people living with PKU remain in significant need of a treatment option that can work for them,” said Dr. Vockley, Chief of Medical Genetics at UPMC Children’s Hospital of Pittsburgh and lead investigator on the study. “These data provide evidence that SYNB1618 can reduce plasma Phe levels in PKU patients with an oral therapy that works locally in the gastrointestinal tract.”

Synlogic also presented data for SYNB1934, the company’s next-generation Synthetic Biotic therapy for the treatment of PKU, in poster presentations during the ICIEM meeting. These presentations demonstrated optimization of the Phe-degrading PAL enzyme contained within SYNB1934 and enhanced Phe consumption activity of SYNB1934 relative to SYNB1618 in healthy volunteers. Synlogic has added an additional arm to the ongoing Phase 2 Synpheny-1 trial to include a cohort of PKU patients treated with SYNB1934.

“These strong results from our Phase 2 study of SYNB1618, along with our emerging preclinical and clinical dataset for SYNB1934 demonstrating an approximate doubling in biomarkers of Phe consumption, provide further validation of the potential for Synthetic Biotic therapies to make a meaningful impact on the lives of patients living with PKU,” said Aoife Brennan, MB, ChB, Synlogic President and Chief Executive Officer. “We look forward to building on these positive interim findings with additional data from Synpheny-1 including both SYNB1618 and SYNB1934 in the first half of 2022 as we advance our PKU program toward an expected Phase 3 study start.”

Phenylketonuria (PKU) is an inherited metabolic disease that manifests at birth and is marked by an inability to break down Phe, an amino acid commonly found in many foods. Left untreated, high levels of Phe become toxic and can lead to serious neurological and neuropsychological problems affecting the way a person thinks, feels, and acts. Due to the seriousness of these symptoms, infants are screened at birth in many countries to ensure early diagnosis and treatment to reduce the risk of intellectual disability and other complications.

SYNB1618 and SYNB1934 are orally administered Synthetic Biotic medicines being developed as potential treatments for phenylketonuria (PKU). They are engineered strains of the microorganism E. coli Nissle that encodes phenylalanine ammonia lyase (PAL), an enzyme that breaks down Phe. They are intended to address the needs of patients of all age groups through the consumption of Phe in the gastrointestinal tract, which has the potential to lower blood Phe levels and enable the consumption of more natural protein in the diet.

Synlogic is bringing the transformative potential of synthetic biology to medicine. With a premiere synthetic biology platform that leverages a reproducible, modular approach to microbial engineering, Synlogic designs Synthetic Biotic medicines that target validated underlying biology to treat disease in new ways. Synlogic’s proprietary pipeline includes Synthetic Biotics for the treatment of metabolic disorders including phenylketonuria (PKU), enteric hyperoxaluria, and homocystinuria. The company is also building a portfolio of partner-able assets in immunology. For more information, visit https://www.synlogictx.com/.