RARE Daily

Synlogic Cuts 21 Percent of Staff as It Initiates Phase 3 Study in PKU

June 5, 2023

Rare Daily Staff

Synlogic said it was cutting 21 percent of its staff to prioritize resources to support its late-stage portfolio of product candidates for rare metabolic diseases as it initiated a phase 3 study of its experimental therapy for the rare metabolic condition phenylketonuria.

Phenylketonuria (PKU) is a rare condition caused by uncontrollable levels of the amino acid phenylalanine (Phe), which can lead to neurocognitive deficits. Despite two approved treatments, approximately 75 percent of patients in the United States remain untreated because they are either unresponsive to current therapies or these options present safety risks. Given that Phe is found in all sources of natural protein, the only option for most patients is a challenging diet virtually free of protein, with supplemental formula requirements for the rest of their lives to try to lower neurotoxic Phe levels.

SYNB1934 is an orally administered, non-systemically absorbed, experimental therapy for PKU, a rare metabolic disease caused by inherited mutations that impair the breakdown of Phe. The goal of PKU management is to reduce plasma Phe below neurotoxic levels, reducing risk of neurocognitive complications. Current treatment options for PKU are limited due to safety and efficacy, leaving the majority of people living with PKU without medical management and with uncontrolled Phe.

Synlogic designed SYNB1934 to target and consume Phe in the GI tract, by applying precision genetic engineering to a well-characterized probiotic. Results to date indicate the potential for SYNB1934 to be the first therapeutic for PKU approved as both a monotherapy and adjunctive medical treatment, and following successful phase 2 results, it has advanced to Synpheny-3, a global, pivotal phase 3 study.

SYNB1934 has received Orphan Drug Designation (ODD) and Rare Pediatric Disease Designation (RPDD) from the FDA in addition to orphan designation from the European Medicines Agency (EMA).

The Synpheny-3 trial will enroll approximately 150 patients with plasma Phe levels at baseline of >360 micrometers. Synpheny-3 will include patients ages 18 years and older. An initial subset of data from patients in Part 1 of the study will be used to assess the opportunity to lower the age of enrollment to 12 years of age. Study participants may follow their usual diet while participating in the trial.

“We have partnered on this pivotal trial design with key stakeholders including clinician experts, global regulatory agencies and people living with PKU and are very grateful for their many insights,” said Aoife Brennan, president and CEO of Synlogic.  In particular, feedback from patients has heightened our sense of urgency to bring forward a new oral therapeutic that can be used either a monotherapy or adjunctive medical treatment.”

In addition to prioritizing it PKU program, the company said it will focus effort on advancing to phase 2 its experimental therapy SYNB1353 for the rare metabolic condition homcystinuria, as well as research activities that support the current clinical pipeline and the ongoing collaboration with Roche.

With the cuts, Synlogic said it expects to extend its cash runway further into the second half of 2024. The company estimates that it will incur approximately $900,000 in costs in connection with the reduction in workforce related to severance pay and other related termination benefits.

Photo: Aoife Brennan, president and CEO of Synlogic



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