Pretzel Therapeutics has presented new preclinical data for its investigational therapy PX578 at the 2026 MDA Clinical and Scientific Conference in Orlando, according to the company. The findings support continued clinical development of the drug candidate for mitochondrial DNA depletion syndromes, including POLG disease, a rare genetic condition that currently has no approved disease-modifying treatments.
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 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 cause of these diseases by increasing mitochondrial DNA levels through activation of the defective POLG enzyme.
According to the company, preclinical studies across multiple 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 markers associated with liver health in the tested models. The therapy demonstrated activity across all tested POLG mutations, including the four most common mutations affecting roughly 70 percent of patients with the condition, the company claims.
Pretzel Therapeutics said the therapy is currently being evaluated in a Phase 1 clinical study involving healthy volunteers that began in 2025. The company expects to complete that study in the first half of 2026 and plans to initiate a Phase 2 clinical trial in individuals living with POLG disease in the second half of the year.
The company develops therapies aimed at restoring cellular energy production to treat neurological, metabolic and rare diseases linked to mitochondrial dysfunction.
