Pretzel Therapeutics

Pretzel Therapeutics is a biotechnology company developing medicines that target novel mechanisms within the mitochondria, the organelles responsible for producing and regulating cellular energy. The company frames its work as "bioenergetics," building a pipeline intended to address high unmet need indications spanning neurological disease, muscular atrophies, metabolic conditions and rare disease. Its stated rationale is that dysfunctional mitochondria are involved in more than 50 diseases, including rare genetic mitochondrial disorders as well as common aging-related conditions such as Alzheimer's and Parkinson's, and that mitochondrial modulation may also be relevant in conditions not directly caused by mitochondrial dysfunction, such as cancer and metabolic disease.

At launch the company described a platform with three primary technology pillars: genome correction, using specialized gene-editing tools to reduce mutated mitochondrial DNA and increase levels of healthy mtDNA; genome expression modulation, using small molecules acting on enzymes involved in mtDNA replication, transcription and translation; and mitochondrial quality control, using small molecules that modulate the organelle's built-in quality control system. More than five research programs were planned at launch.

By April 2025 the pipeline was organized into franchises. The bioenergetics restoration franchise is led by PX578, a small molecule activator of mitochondrial DNA polymerase (POLG) positioned for mitochondrial DNA depletion syndromes (MDDS) and broader neurodegenerative disease; it entered Phase 1. The energetics modulation franchise is led by a POLRMT program targeting mitochondrial RNA polymerase for metabolic conditions including obesity, described as being in late preclinical development.

Founding story

The company was founded by three academic researchers in mitochondrial biology — Claes Gustafsson (professor of medical biochemistry, University of Gothenburg), Michal Minczuk (Group Leader and MRC Investigator, MRC Mitochondrial Biology Unit, University of Cambridge), and Nils-Göran Larsson (professor of mitochondrial genetics, Karolinska Institutet) — together with Gabriel Martinez and Paul Thurk, who played formative roles based on biotechnology industry experience. The company also credits Gunther Kern, Jeremy Green and Christina Trojel-Hansen for contributions to its formation. Its name is a reference to the twisted shape of mitochondria.

Business model

Pretzel operates as a preclinical-to-clinical stage drug developer, funding internal discovery and development of proprietary therapeutic candidates through venture financing and, in at least one case, non-dilutive grant funding from a disease charity. No product revenue or commercial partnerships are described in the sources.

Traction

Raised a $72.5 million Series A at launch in September 2022 with plans for more than five research programs. As of April 2025, PX578 had entered Phase 1 clinical testing in healthy adults with a patient trial in MDDS planned for 2026, and a second lead program targeting POLRMT was in late preclinical development. The company also secured grant funding from Parkinson's UK.

Latest developments

On April 3, 2025 Pretzel announced initiation of recruitment in a randomized, double-blind, placebo-controlled Phase 1 study of PX578, evaluating safety, tolerability and pharmacokinetics of single and multiple ascending doses in healthy adults, with a potential MDDS patient trial in 2026. Concurrently it announced grant funding from Parkinson's UK to evaluate its POLG activation mechanism in Parkinson's disease models with Dr. Roberta Filograna's lab at the Karolinska Institute.