- Fast Track Designation adds to recent regulatory momentum for PX578 -
- Phase 2 (POLARIS) study initiation planned for late 2026 -
WALTHAM, Mass.--(BUSINESS WIRE)--#ClinicalTrials--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 U.S. Food and Drug Administration has granted Fast Track Designation to PX578 for the treatment of POLG-mediated primary mitochondrial disorders (POLG disease), a rare, progressive genetic condition for which there are currently no approved disease-modifying treatments.
"Receiving Fast Track Designation is an important regulatory milestone for PX578 and further underscores the urgent need for new treatment options for people living with POLG disease," said Ashish Dugar, Chief Development Officer of Pretzel Therapeutics. “As we prepare to initiate the POLARIS study in patients, we remain focused on generating the clinical evidence needed to advance PX578 and bring a potentially disease-modifying therapy to individuals impacted by this progressive and debilitating disease."
This designation follows recently announced FDA clearance to initiate a first-in-patient clinical trial of PX578, the Company’s lead therapeutic candidate. POLARIS (POLg Activation and Recovery In Subjects) will evaluate PX578 in adult patients with POLG disease building on recent success with a Phase 1 healthy volunteer study with PX578 conducted in New Zealand.
FDA Fast Track designation reflects the significant unmet medical need in POLG disease and supports ongoing engagement with FDA as Pretzel advances PX578 toward Phase 2 study initiation. The designation provides opportunities for more frequent FDA interactions during development and potentially expedites review of PX578.
About POLG-mediated Primary Mitochondrial Disorders
POLG-mediated primary mitochondrial disorders (POLG disease) are progressive, multisystem conditions 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 disorders, 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.
Contacts
Media contact
Gina Nugent
gina@nugentcommunications.com
Clinical contact
Clinical@pretzeltx.com
Business Development contact
Baruch Harris, Ph.D., Chief Operating Officer
baruch.harris@pretzeltx.com
