A Major Step Forward for the Global POLG Community

2 Sep, 2026

FDA clears PX578 to enter Phase 2 clinical testing

At IMP, few moments bring more hope than seeing innovative science move closer to real treatment options for our community.

The FDA has now cleared Pretzel Therapeutics’ IND application for PX578, allowing the therapy to advance into a Phase 2 clinical study (POLARIS) for people living with POLG‑mediated mitochondrial disease.

Photo of 8 glass test tubes in a rack. They contain liquid. They are positioned against a green background.

For a condition with no approved disease‑modifying treatments, this marks a meaningful shift.

PX578 is especially promising because it targets the root cause of POLG disease: it is a CNS‑penetrant small molecule designed to activate POLγ and support mitochondrial DNA replication. Moving directly into Phase 2 reflects both urgency and potential — and offers families a renewed sense of possibility.

To Pretzel Therapeutics, and to the researchers, clinicians, regulators, advocates and families who helped pave the way: thank you. Clinical progress is always a shared effort.

IMP will continue ensuring the global patient voice is embedded throughout drug development, trial design and future access planning. We will be watching the progress of POLARIS with deep hope.