Mitochondrial drugs, with a twist: Pretzel Therapeutics launches with $72.5M in funding

With a name like Pretzel Therapeutics, some may think the fledgling biotechnology company specializes in baking.

The startup, officially launched Monday by a trio of European mitochondrial biology researchers, is instead looking at rare genetic disorders and diseases of aging such as Alzheimer’s and Parkinson’s.

With $72.5 million in Series A funding, Pretzel plans to advance more than five research programs using technologies that involve gene editing as well as control mitochondrial gene expression and health.

Pretzel’s name was inspired by the shape of mitochondria, which resembles the twists of the German bread.

A mitochondrion supplies cells with the power they need to survive. They turn the energy the body gets from food into fuel that cells use for a variety of chemical reactions.

When their DNA, or mtDNA, mutates in certain ways, mitochondria produce less energy, preventing cells from functioning properly. Mitochondrial dysfunction is the cause of dozens of rare genetic diseases, and is thought to be a factor in common age-related disorders such as Alzheimer’s.

Pretzel’s scientists aim to use gene editing to remove mutated mtDNA that other genome manipulation techniques such as CRISPR can’t reach because of the organelle’s tiny size, said Jay Parrish, Pretzel’s CEO.

The company also hopes to control mitochondrial genome expression by targeting with small molecule drugs the enzymes involved in mtDNA replication, transcription and translation. Small molecule drugs might also be used to tweak the mitochondria’s systems for quality control.

A handful of other companies are focused on mitochondrial diseases. Stealth BioTherapeutics, which until recently traded under the stock ticker “MITO,” is one of the most advanced, with a drug candidate in late-stage testing. But it’s hit several significant setbacks, falling short in a previous Phase 3 study and getting a drug application rejected by the Food and Drug Administration.

Elsewhere, Mitobridge, a biotech bought by Astellas in 2017, is in clinical testing with two drugs. Vincere Biosciences is researching small molecules to improve mitochondrial quality, while Reneo Pharmaceuticals is developing drugs to treat rare genetic diseases caused by mitochondrial dysfunction.

But Pretzel claims it is looking at mitochondrial disease more broadly than others in the field.

“​​People have been working with the mitochondria for a long time but this is a different approach,” Parrish said. “The mitochondria itself is an amazing organelle that does all these cool things beyond just energy production. There are drugs that hit it, but it has untapped potential.

The company will consider raising another round of private funding in one to two years, but Parrish declined to say when it expects to advance a drug into the clinic. By then, Pretzel also hopes to have begun research on how its platform can treat diseases that aren’t directly caused by mitochondrial dysfunction, such as rare cancers.

Arch Venture Partners and Mubadala Capital first began building Pretzel in early 2020, aiming to create a platform biotech company. Then, Paul Thurk, the Arch partner leading the project, suddenly died in January 2021.

Three investors — Parrish, Arch managing director Kristina Burow and Mubadala executive director Alaa Halawa — forged on with the project in honor of Thurk.

“We were able to recover due to the team who are not just great scientists or great investors, but really great people,” said Gabriel Martinez, one of Pretzel’s directors.

Pretzel will be based in Waltham, Mass. with a research facility in Gothenburg, Sweden.

Arch and Mubadala, a sovereign venture capital fund from the United Arab Emirates, invested $15 million apiece in the company. GV, Invus and Angelini Ventures filled out the round along with more than half a dozen other investors.

Though Pretzel isn’t disclosing exactly which diseases it’s targeting, its investors see a wide range of possibilities.

“We’re more intrigued and excited by the hard-to-reach fruits like Alzheimer’s and diabetes, which we believe this company is poised to address,” Halawa said.

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