Promising Data on Phenylketonuria, Homocystinuria Therapies Presented at SIMD

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“We have now seen consistently across the program the potential to quite meaningfully reduce Phe levels in patients with PKU," lead investigator Dr. Jerry Vockley says in a statement.

Full clinical data from Synlogic’s phase 2 study on phenylketonuria (PKU) and phase 1 study on homocystinuria (HCU) were presented at the Society for Inherited Metabolic Disorders (SIMD) 44th Annual Meeting. The positive results support the prospect that synthetic biotics may be able to help address unmet treatment needs for these rare metabolic conditions.1

SYNB1934 and SYNB1353 are orally administered therapeutics that function based on the pathophysiology of the disease by genetically engineering probiotic bacteria. The study findings yielded evidence of phenylalanine (Phe) metabolism by SYNB1934 in all patients, based on production of strain specific biomarkers, and a plasma Phe reduction of -53% among responders (defined as >20% reduction in Phe from baseline); response rate was 60% (3 of 5 patients).

Additionally, one patient who was taking sapropterin dihydrochloride (Kuvan) at baseline achieved an additional reduction in plasma Phe of -80% as compared with baseline. Adverse events were mostly gastrointestinal-related, consistent with those associated with a probiotic, and were mild or moderate.

“As the lead investigator for Synlogic’s PKU phase 2 Synpheny-1 study, I was pleased to see the significant levels of interest in the additional results from the study presented during the SIMD meeting,” Jerry Vockley, MD, PhD, University of Pittsburg said in a statement. “We have now seen consistently across the program the potential to quite meaningfully reduce Phe levels in patients with PKU. I very much look forward to assessing this more broadly in the phase 3 study, given the significant need for new treatment options for those living with PKU.”

Synlogic stated that there are plans to advance SYNB1934 into a phase 3 study for PKU, and SYNB1353 into a phase 2 study for HCU in 2023.

Previously reported data from the phase 2 study included 20 patients with PKU, 11 of which were enrolled in the SYNB1618 arm, and 9 were enrolled in the SYNB1934 arm. Investigators observed reductions in fasting plasma Phe that demonstrated clinically meaningful reductions in both strains.2

The mean change from baseline on day 14 was -20% for SYNB1618 and -34% for SYNB1934. Results across all measured indicators of activity for both drug candidates were consistent, including plasma D5-Phe, plasma D5-TCA and urinary D5-HA, with numerically greater changes observed for SYNB1934.

References:

  1. Synlogic Announces Data Presentations at the Society for Inherited Metabolic Disorders (SIMD) 44th Annual Meeting. News release. Synlogic Therapeutics. March 20, 2023. Accessed March 20, 2023. https://investor.synlogictx.com/news-releases/news-release-details/synlogic-announces-data-presentations-society-inherited
  2. Synlogic Announces Positive Top-Line Phase 2 Data for Phenylketonuria (PKU); SYNB1934 Advances to Phase 3. News release. Synlogic Therapeutics. October 22, 2022. Accessed March 20, 2023. https://investor.synlogictx.com/news-releases/news-release-details/synlogic-announces-positive-top-line-phase-2-data
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