On September 12, Pretzel Therapeutics, a biotechnology company, announced the completion of a $72.5 million Series A financing to pioneer innovative therapies that modulate mitochondrial function. This round of financing was led by ARCH Venture Partners and Mubadala Capital, with participation from HealthCap, Cambridge Innovation Capital, and GV.
Massachusetts-based Pretzel, which aims to exploit the complexities of mitochondrial biology to develop breakthrough therapies, has a research facility in Gothenburg, Sweden. The company was founded by leading academic experts in mitochondrial biology, including mitochondrial gene expression expert Dr. Claes Gustafsson from the University of Gothenburg, mitochondrial genome engineering expert Dr. Dr. Nils-Göran Larsson, Professor of Mitochondrial Genetics at Karolinska Institute. The company has been backed by a world-class investment group.
Mitochondrial dysfunction is the root cause of many diseases. Because mitochondria are important energy-converting organelles, dysfunctions affecting mitochondrial pathways can have widespread effects throughout the body. Dysfunctional mitochondria are implicated in more than 50 diseases, which can be broadly divided into primary mitochondrial diseases and secondary mitochondrial diseases.
Primary mitochondrial diseases are a group of rare genetic disorders that affect individuals of all ages. Some examples of diseases include MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes), NARP (neuropathy, ataxia, and retinitis pigmentosa), Leigh syndrome, Leber hereditary optic neuropathy, mitochondrial neurogastrointestinal encephalopathy Myopathy and Alpers. And many diseases that are not usually considered mitochondrial diseases but still show signs of mitochondrial involvement, so-called secondary mitochondrial dysfunction, which can be inherited or acquired (such as in response to environmental exposures) . Diseases involving such problems include neurodegenerative diseases such as Alzheimer’s and Parkinson’s, as well as autoimmune diseases such as multiple sclerosis and lupus. Secondary mitochondrial disease is also one of the most important contributors to aging as mutations in mitochondrial DNA accumulate over time. Furthermore, modulating mitochondrial biology offers a potential approach to treat diseases not directly caused by mitochondrial dysfunction, such as cancer and metabolic diseases.
Pretzel’s platform contains 3 primary technologies for regulating mitochondrial function:
1) Genome correction therapy will utilize specialized gene editing tools to reduce mutant mitochondrial DNA and increase the level of healthy mitochondrial DNA;
2) Genome expression regulation will be achieved by small molecules acting on mitochondrial DNA replication, transcription and translation-related enzymes;
3) Finally, mitochondrial quality control will be achieved through the use of small molecules that modulate the mitochondrial built-in quality control system.
Co-founder Claes Gustafsson said: “Mitochondria have historically been a challenging organelle for therapeutic targeting, in part because mitochondrial diseases are extremely genetically and phenotypically diverse, but also due to the unique features of mitochondrial genome function. However, in recent years, The industry’s scientific understanding of mitochondrial biology has advanced significantly, leading to new insights into their role in many epidemics and how they can be targeted by therapy. Excited to form Pretzel to translate these insights for therapies that can meaningfully improve people’s lives.”
Alaa Halawa, Partner at Mubadala Capital, said: “Pretzel is developing a first-of-its-kind platform to modulate mitochondrial biology with a wide range of potential applications in rare and common diseases. We are proud to co-lead the company’s Series A financing and partner with Pretzel to build a world-leading center of excellence for mitochondrial dysfunction diseases.”
