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Pretzel Therapeutics launches to advance mitochondria-based therapies

Among the tools in the company’s arsenal is gene editing of mitochondrial DNA

by Shi En Kim
September 12, 2022

Headshots of Pretzel's chairman and CEO Jay Parrish on the left and chief scientific officer Gabriel Martinez on the right.
Credit: Heidi Kalpak of Pink Peach; Gigi de Manio Photography
Pretzel Therapeutics' chairman and CEO Jay Parrish (left) and chief scientific officer Gabriel Martinez (right)

Pretzel Therapeutics has launched today with $72.5 million in series A funding. The new company’s name alludes to the squiggly membrane folds within the organelle it targets: the mitochondria.

Mitochondria are often called the powerhouses of the cell because they produce the energy molecule adenosine triphosphate (ATP) via the oxidative phosphorylation chemical reaction. They also carry their own DNA that is distinct from the DNA in the cell’s nucleus. Given their fundamental function within each cell in the body, mitochondria are implicated in a broad swath of diseases, including cognitive disorders, cancer, and aging-related ailments.

Mitochondria “support all of the body’s functions,” says Marni Falk, a clinical geneticist at the Children’s Hospital of Philadelphia. “If there’s a problem in the mitochondria, the organs don’t work.” This makes them important pharmacological targets, she says.

Pretzel Therapeutics aims to treat mitochondrial dysfunction using three approaches: editing the mitochondrial genome, regulating mitochondrial gene expression, and what chairman and CEO Jay Parrish calls “mitochondrial quality control”—regulating production and sorting of mitochondria so defective ones are sent to the cell’s disposal system. The company will deploy small molecules for the latter two approaches.

According to its leadership team, Pretzel Therapeutics stands out from other mitochondria-targeting companies because it’s working at the early stages where mitochondria go haywire: at the gene and gene expression level. By regulating the genes rather than the oxidation-phosphorylation process as many other companies do, Parrish says, Pretzel hopes that their strategies can better modulate mitochondrial behavior.

The Waltham, Massachusetts–headquartered firm also hopes to be the first to conduct mitochondrial gene editing in humans. “People have edited the mitochondria, but we hope to be the first to do it clinically,” Parrish says.

The company is currently advancing six programs through the preclinical stage. Given the breadth of mitochondrial diseases, the company hasn’t chosen a specific disorder to address and is not disclosing any of its targets right now.



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