The United Mitochondrial Disease Foundation’s (UMDF) venture philanthropy arm, The Mito Fund, has invested in Pretzel Therapeutics, a Massachusetts-based company with research facilities in Mölndal , Sweden, focused on harnessing cellular energetics to modulate disease processes and improve survival, function and quality of life for a breadth of conditions.

PX578, the lead development program in Pretzel’s bioenergetics portfolio, recently entered Phase 1 clinical development in the U.S. The therapy’s focus is restoring function to mutant mitochondrial DNA polymerases, allowing repopulation of depleted mtDNA, and offering a promising approach for the treatment of mitochondrial DNA polymerase disorders (commonly known as POLG disorders) and other severe conditions linked to mtDNA depletion.

POLG-related mitochondrial diseases typically affect multiple organs, including the brain, nerves, muscles, liver, and vision. It is one of the most common inherited mitochondrial diseases, with estimates it affects 1 in 10,000 patients. There is no FDA-approved therapy for any POLG-related mitochondrial disease.

“The collective disease types targeted by PX578 represent some of the most common and relentlessly progressive forms of mitochondrial disease. There still remains much for Pretzel to do, but ultimately an approval would meet a huge unmet need in our community,” said UMDF’s Science and Alliance Officer Dr. Philip Yeske.

“We are honored to receive this investment from The Mito Fund, whose commitment to improving the lives of patients living with mitochondrial disease aligns deeply with our mission,” said Gabriel Martinez, Ph.D., Chief Scientific Officer and Co-Founder of Pretzel Therapeutics. “This funding not only validates the promise of our scientific approach, but also supports development of PX578, the lead therapeutic in our energetics restoration franchise, with disease modifying potential across rare mtDNA depletion syndromes and broader degenerative diseases.”

Like all investments made by The Mito Fund, the Pretzel Therapeutics consideration went through a rigorous review process by UMDF’s Venture Philanthropy Investment Committee, an advisory group consisting of world-class experts in the areas of mitochondrial disease, pharmaceutical development, and private equity investments. After receiving the committee’s recommendation, the investment was then approved by UMDF’s full Board of Trustees.

“We received tremendous feedback from our committee when it comes to the potential of PX578,” said Dr. 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. If we’re ever going to get to an approved therapy, that’s a critical component, and we look forward to deepening the relationship with Pretzel.”

Launched in the summer of 2023, The Mito Fund is UMDF’s effort to ramp up the development of mitochondrial disease treatments and cures. The fund’s venture philanthropy model is designed not only to financially support the development of the next generation of mitochondrial disease treatments, but also to leverage UMDF’s experience and network to accelerate the development process and lower the risk associated with entry into the field for a wide range of investors and researchers.

Other companies in The Mito Fund portfolio include:

• Napigen Therapeutics, a company that aims to harness the potential of mitochondria to impact human healthcare with its unique organelle genome editing tools.
• Pierrepont Therapeutics, a company focused on advancing to the clinic a proprietary intracellular enzyme replacement therapy for Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE)
• Khondrion, a clinical-stage biopharmaceutical company focused on discovering and developing therapies targeting primary mitochondrial disease (PMD). Khondrion’s lead asset sonlicromanol is in clinical development to improve fatigue (lack of energy), muscle weakness, and other symptoms in people living with m.3243A>G Primary Mitochondrial Disease, including classic MELAS, MIDD and Multi-system Phenotypes.