Pretzel Therapeutics presented new preclinical data for its investigational treatment PX578 at the 2026 MDA Clinical and Scientific Conference in Orlando, according to the company. The findings support the continued clinical development of a drug candidate for mitochondrial DNA depletion syndromes, including POLG disease, a rare genetic condition that currently has no approved disease-modifying therapies.
PX578 is described by the company as a first-in-class small molecule designed to activate mitochondrial DNA polymerase gamma, also known as POLG. Mutations in the genes responsible for maintaining mitochondrial DNA can lead to mitochondrial DNA depletion syndromes, a group of disorders that affect energy production in cells and can cause severe neurological, muscular and metabolic symptoms. The company states that PX578 aims to address the underlying causes of these diseases by increasing levels of mitochondrial DNA by activating the defective enzyme POLG.
According to the company, preclinical studies in several in vitro and in vivo disease models showed that PX578 increased mitochondrial DNA levels and improved cellular respiration and energy production. The company also reported improvements in survival outcomes and symptoms related to liver health in the models tested. The company claims the treatment showed activity across all POLG mutations tested, including the four most common mutations that affect about 70 percent of patients with the disease.
Pretzel Therapeutics said the treatment is currently being evaluated in a Phase 1 clinical study involving healthy volunteers, which will begin in 2025. The company expects to complete this study in the first half of 2026 and plans to start a phase 2 clinical trial in POLG patients in the second half of the year.
The company develops therapies aimed at restoring cellular energy production to treat neurological, metabolic and rare diseases associated with mitochondrial disorders.
