Pretzel Therapeutics aims to restore cellular energetics and treat degenerative diseases influenced by mitochondrial dysfunction.
US biotech Pretzel Therapeutics has secured investment from The Mito Fund, the venture philanthropy initiative of the United Mitochondrial Disease Foundation (UMDF). Based in Massachusetts, with research operations in Sweden, Pretzel is developing treatments targeting mitochondrial diseases, particularly those associated with mutations of the POLG gene and mitochondrial DNA (mtDNA) depletion syndromes. Financial details of the investment were not disclosed.
Mitochondrial diseases encompass a diverse range of genetic and phenotypic disorders, affecting cellular bioenergetics and often leading to systemic effects across the brain, muscles, liver and other organs. Pretzel, which secured a $72.5 million Series A in 2022, is developing a pipeline of therapeutics that intervene at the level of mitochondrial function by modulating the replication and transcription of mtDNA. This approach is intended to restore cellular energetics and arrest or reverse disease progression in disorders influenced by mitochondrial dysfunction, including age-related diseases.
Pretzel’s lead therapeutic candidate, PX578, currently in Phase 1 clinical development, is designed to activate the mitochondrial DNA polymerase POLG and restore mtDNA levels and functional capacity in cells affected by mtDNA depletion. The company claims the strategy has potential applications across a broad spectrum of degenerative diseases, particularly those marked by severe energy deficits at the cellular level, such as neurodegenerative diseases.
In addition to PX578, Pretzel’s development pipeline includes a second program targeting the mitochondrial RNA polymerase POLRMT. The liver-targeted intervention, currently in late preclinical development, is being evaluated as a treatment for metabolic diseases, including obesity, through modulation of cellular energy production.
The Mito Fund, launched in 2023, is designed to accelerate the development of treatments and cures for mitochondrial diseases through a venture philanthropy model. The fund’s approach leverages UMDF’s scientific network and patient community to support developers.
“The collective disease types targeted by PX578 represent some of the most common and relentlessly progressive forms of mitochondrial disease,” said UMDF’s Dr Philip Yeske. “There still remains much for Pretzel to do, but ultimately an approval would meet a huge unmet need in our community.”
The investment by The Mito Fund followed an intensive evaluation by UMDF’s Venture Philanthropy Investment Committee, which includes specialists in mitochondrial science, pharmaceutical development and private equity.
“We received tremendous feedback from our committee when it comes to the potential of PX578,” added Yeske. “But in our conversations with Pretzel, the thing that also excited us was the company’s commitment to partnering with patient advocacy groups like UMDF to advance broad POLG-related research.”
In addition to Pretzel Therapeutics, The Mito Fund has invested in several other promising companies, including Napigen Therapeutics, which is building mitochondrial genome editing tools; Pierrepont Therapeutics, which is developing enzyme replacement therapies; and Khondrion, a clinical-stage company advancing treatments for primary mitochondrial diseases.
