Pretzel Therapeutics has received authorisation from the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) to proceed with a clinical trial of PX578 in patients with POLG-mediated primary mitochondrial disorders.
The company expects to begin the Phase II study by the end of 2026.
Go deeper with GlobalData
Discover B2B Marketing That Performs
Combine business intelligence and editorial excellence to reach engaged professionals across 36 leading media platforms.
The MHRA’s authorisation of the company’s clinical trial application marks the third regulatory milestone for PX578 in recent months.
In August 2026, the US Food and Drug Administration (FDA) cleared an investigational new drug (IND) application for PX578 and granted fast track designation for the treatment of POLG-mediated primary mitochondrial disorders in September.
Pretzel Therapeutics chairman and CEO Jay Parrish said: “Receiving UK authorisation following FDA clearance of our IND represents an important milestone for PX578 and for our efforts to bring a potential disease-modifying treatment to people living with POLG-mediated mitochondrial disorders.”
POLG disease is a rare, progressive genetic condition caused by mutations in the POLG gene, which plays a central role in mitochondrial DNA replication and maintenance.
No approved therapies currently target the underlying cause of the disease.
The planned trial, named POLg Activation and Recovery In Subjects (POLARIS), is a randomised, double-blind, placebo-controlled Phase II study. It is designed to assess PX578’s tolerability, safety, pharmacokinetics, pharmacodynamics and clinical efficacy in adults with POLG disease.
PX578 is a small molecule designed to activate POLG and increase mitochondrial DNA levels.
The company describes it as a CNS-penetrant molecule intended to enhance mitochondrial function. Its stated goal is to restore mitochondrial activity and potentially modify the underlying disease process.
Preclinical investigations utilising various in vitro and in vivo models, along with a recently concluded Phase I study involving healthy volunteers, substantiate the disease-modifying capabilities of PX578 and its progression into Phase II clinical trials for patients diagnosed with POLG disease.
