Pretzel Therapeutics Receives UK Regulatory Authorization to Advance PX578 Into Clinical Development in Patients for the Treatment of POLG-Mediated Primary Mitochondrial Disorders
Regulatory milestone follows U.S. FDA clearance of Investigational New Drug application in August 2026 Initiation of
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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, today 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.
About POLG-mediated Primary Mitochondrial Disease
POLG-mediated primary mitochondrial disease (POLG disease) is a progressive, multisystem disorder caused by impaired cellular energy production due to mitochondrial DNA (mtDNA) depletion. It represents one of the most common forms of mitochondrial DNA depletion syndromes (MDDS) yet remains considerably underdiagnosed or misdiagnosed. The disease affects individuals across all ages, with presentation and prognosis largely determined by age of onset: childhood-onset (prior to age 12) is severe and rapidly progressive, characterized by liver involvement, seizures, and cognitive regression; juvenile and adult-onset (ages 12-40) often presents with ataxia, peripheral neuropathy, and seizures; and late-onset (ages 40+) is typically more slowly progressive, characterized by ophthalmoplegia, ptosis, and myopathy. Across all forms, POLG disease is highly debilitating and associated with substantial morbidity and early mortality. There are currently no disease-modifying therapies, underscoring a critical and urgent need for treatments that address the underlying mitochondrial dysfunction.
About PX578
PX578 is a first-in-class, CNS penetrant small molecule activator of the mitochondrial polymerase POLG designed to increase mitochondrial DNA (mtDNA) levels, enhance mitochondrial function and improve quality of life by halting or reversing disease progression across mitochondrial disorders, including POLG-mediated primary mitochondrial disease, a rare and often devastating condition for which no approved disease-modifying therapies currently exist. Preclinical studies across multiple in vitro and in vivo models, as well as a recently completed Phase 1 healthy volunteers study, support the disease-modifying potential of PX578 and its advancement into Phase 2 clinical evaluation in patients with POLG disease.
About Pretzel Therapeutics
Pretzel Therapeutics, a clinical-stage biotechnology company building a deep, first-in-class pipeline of novel medicines designed to restore mitochondrial function, improve cellular energetics and impede disease progression across a range of neurological and rare diseases. The Company’s lead therapeutic candidate, PX578, is expected to enter Phase 2 clinical study for individuals with POLG disease in late 2026. The company is headquartered in Waltham, MA, and has research facilities in Mölndal, Sweden. For more information, visit www.pretzeltx.com.
Forward-Looking Statements
This press release contains “forward-looking statements” that involve substantial risks, assumptions, and uncertainties. Forward-looking statements are often identified by the use of words such as, but not limited to, “believe,” “estimate,” “intend,” “may,” “plan,” “potentially,” “will,” “expect,” “enable,” “likely” or the negative of these terms or other similar expressions. All statements, other than statements of historical facts, regarding management’s expectations, beliefs, goals, plans or Pretzel’s prospects should be considered forward-looking statements. Readers are cautioned that actual results may differ materially from projections or estimates due to a variety of important factors. These forward-looking statements are made as of the date of this presentation, and Pretzel assumes no obligation to update the forward-looking statements, or to update the reasons why actual results could differ from those projected in the forward-looking statements, except as required by law.
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