Pretzel Therapeutics, Inc., a clinical-stage biotechnology company advancing a new class of medicines designed to restore mitochondrial function, improve cellular energetics and impede disease progression across a range of neurological and rare diseases, announced that the Medicines and Healthcare products Regulatory Agency (MHRA) has authorized the company’s clinical trial application for PX578, the company’s lead therapeutic candidate being developed for patients with POLG-mediated mitochondrial disorders (POLG disease), a rare, progressive genetic disorder caused by mutations in the POLG gene causing a depletion of mitochondrial DNA.

UK authorization follows clearance by the U.S. Food and Drug Administration (FDA) of the Investigational New Drug (IND) application for PX578 in August 2026 and FDA Fast Track Designation for PX578 for the Treatment of POLG-mediated Primary Mitochondrial Disorders in September 2026, marking the third major regulatory milestone for the program and supporting the company’s plans to advance global clinical development of the Phase 2 POLARIS (POLg Activation and Recovery In Subjects) study, evaluating PX578 in adult patients with POLG disease.

“For people living with POLG disease, the need for effective treatments is profound, and the lack of disease-modifying options leaves patients and families facing progressive disease with very few options,” said Professor Sir Doug Turnbull, Emeritus Professor of Neurology, Newcastle University. “Advancing therapies that have the potential to address the underlying biology of POLG disease represents an important step for the field. The clinical development of PX578 is particularly encouraging, and I look forward to seeing its potential evaluated in patients.”

PX578 is designed to activate POLG and increase mitochondrial DNA (mtDNA), with the goal of restoring mitochondrial function and potentially modifying the underlying disease process. POLG disease is a rare, progressive and potentially life-threatening group of disorders caused by genetic variants affecting POLG, a key enzyme involved in mitochondrial DNA replication and maintenance. There are currently no approved disease-modifying therapies specifically targeting the underlying cause of POLG-mediated disease.

“Receiving UK authorization 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,” said Jay Parrish, Ph.D., Chairman and Chief Executive Officer of Pretzel Therapeutics.

“With regulatory pathways now cleared in both the U.S. and UK, we are focused on advancing our Phase 2 POLARIS study and working toward initiating clinical development in patients by year end 2026,” said Ashish Dugar, Ph.D., Chief Development Officer of Pretzel Therapeutics.”

POLARIS is a randomized, double-blind, placebo-controlled Phase 2 trial designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and clinical efficacy of PX578 in adults with POLG disease.

The company expects to initiate the Phase 2 study by the end of 2026.