Pretzel Launches with $72.5 Million in Funding to Pioneer Mitochondrial Therapies

Pretzel Therapeutics launched with a $72.5 million in a series A financing to pioneer novel therapies to modulate mitochondrial function to treat rare and common diseases, taking its name from the shape of its target.  

ARCH Venture Partners and Mubadala Capital led the financing with participation from HealthCap, Cambridge Innovation Capital, Cambridge Enterprise, Angelini Ventures, GV, Invus, Eir Ventures, GU Ventures, and Karolinska Institutet Holding.

Jay Parrish, a venture partner at ARCH Venture Partners and co-founder of ROME Therapeutics will lead the new company. Parrish most recently co-founded and served as the CEO of Vir Biotechnology, where he helped lead the company as its first employee through its IPO and first drug approval.

“We are excited to pioneer a new era in the treatment of diseases related to mitochondrial dysfunction. The expertise we have assembled and the platform technologies we have created will allow new inroads into treating both rare genetic diseases as well as common diseases of aging,” said Jay Parrish, chairman of the Board and CEO of Pretzel.

Dysfunctional mitochondria are involved in more than 50 diseases. The most severe of these are broadly termed mitochondrial diseases, a group of rare genetic conditions which affect individuals of all ages. Mitochondrial dysfunction also plays an important role in more common diseases, including aging-related disorders such as Alzheimer’s and Parkinson’s diseases. In addition, modulating mitochondrial biology presents a potential approach to the treatment of diseases not directly caused by mitochondrial dysfunction, for instance cancer and metabolic diseases.

Pretzel’s platform encompasses three primary technologies to modulate mitochondrial function: genome correction, genome expression modulation, and mitochondrial quality control. The company’s genome correction therapeutics will utilize specialized gene-editing tools to reduce mutated mitochondrial DNA and increase the levels of healthy mitochondrial DNA. Genome expression modulation will be accomplished using small molecules that act on the enzymes involved in mitochondrial DNA replication, transcription, and translation. Finally, mitochondrial quality control will be targeted using small molecules that modulate mitochondria’s built-in quality control system.

“Pretzel is advancing a first-of-its-kind platform to modulate mitochondrial biology, with a vast range of potential applications across rare and common disorders,” said Alaa Halawa, partner and head of the U.S. ventures business at Mubadala Capital.

Pretzel’s founders include three leading academics in the field of mitochondrial biology: Claes Gustafsson, professor of medical biochemistry at the University of Gothenburg and an expert in mitochondrial gene expression; Michal Minczuk, group leader and MRC investigator at the MRC Mitochondrial Biology Unit, University of Cambridge and an expert in mitochondrial genome engineering; and Nils-Göran Larsson, professor of mitochondrial genetics at the Department of Medical Biochemistry and Biophysics at Karolinska Institutet who has published more than 150 articles on mitochondrial biology.

In addition to Gustafsson, Minczuk, and Larsson, founders Gabriel Martinez and Paul Thurk played a formative role in the company’s creation based on their deep biotechnology industry expertise. Gunther Kern, Jeremy Green, and Christina Trojel-Hansen also contributed to the formation of Pretzel.

“Mitochondria have historically been a challenging cellular organelle to target therapeutically, in part because mitochondrial diseases are extremely diverse, both genetically and phenotypically, but also due to the distinctive characteristics of mitochondrial genome function. However, scientific understanding of mitochondrial biology has greatly advanced in recent years, allowing new insights into their role in many prevalent diseases, as well as how they can be therapeutically targeted,” said Claes Gustafsson. “It’s gratifying to form Pretzel to translate these insights into therapies that could meaningfully improve people’s lives.”

Photo: Jay Parrish, chairman of the Board and CEO of Pretzel