Freshly baked: Pretzel Therapeutics takes out the oven mitts to drug diseases in the powerhouse of the cell
12 Sep 2022
Cell TherapySmall molecular drugEmergency Use AuthorizationCollaborate
After helping co-found Vir Biotechnology and lead the biotech’s business development through the first few years, including a rare emergency use authorization for a Covid-19 treatment, Jay Parrish has found a new home at the pretzel powerhouse.
Focused on the so-called powerhouse of the cell, the mitochondria, Pretzel Therapeutics emerged Monday with $72.5 million in Series A backing from ARCH Venture Partners and Mubadala Capital, along with a syndicate of other investors.
Parrish told Endpoints News earlier this year the company would reel in a round “in the middle” of the relatively small $20 million rounds that ARCH sometimes writes seed checks for and the megarounds it has backed, including the $500 million Series A at Parrish’s former employer, Vir.
Exclusive: ARCH and GV are building a large startup focused on mitochondrial diseases
As the CEO and chairman, Parrish is leading a team of 35 to go after three principal areas: genome correction, genome expression modulation and mitochondrial quality control to regulate the outputs of the waste disposal system, he told Endpoints ahead of the official unveiling. The first will be done via gene editing and the other two will seek out small molecule routes, Parrish said.
CRISPR and certain other gene editing tools don’t always fit the bill when it comes to mitochondrial DNA (mtDNA). So, Pretzel is targeting zinc-finger nucleases delivered by adeno-associated viruses, as described in a co-founder’s paper, to squash mutated mtDNA and leave room for healthy copies to blossom.
“Of the six different programs, we are at lead generation in several of them,” Parrish said. “We are now lead optimization on a couple, as well, so we hope to be in the clinic in the next couple of years and really answer some of these hypotheses.”
Up first will be so-called primary mitochondrial diseases, mainly rare genetic disorders, the CEO said, characterizing the 50-plus diseases as “alphabet soup.” The mitochondria “touches everything,” and diseases of the powerhouse can lead to muscle weakness, cognitive defects, brain degeneration and other symptoms in about 1 in 5,000 people worldwide, according to Parrish.
Secondary mitochondrial diseases will populate the pipeline once the thesis is proven out in initial human testing. That second batch includes the likes of Parkinson’s, Alzheimer’s, cancer and metabolic disorders, he said.
“I was hot to trot when I learned about what this company was working on, so I jumped in,” Parrish said. “But as far as where the field is at, recent discoveries, especially by our founders, has created a critical mass of tools to help drug the mitochondria.”
The ARCH venture partner paints the field as having made an “unparalleled leap in understanding the biology of the mitochondria” in recent years, pointing to the labs of the startup’s founders as examples.
Preview
Source: Endpts
Claes Gustafsson
Pretzel’s underpinnings come from the academic world of University of Gothenburg professor Claes Gustafsson; Michal Minczuk, an MRC Mitochondrial Biology Unit investigator at University of Cambridge; and Karolinska Institutet professor Nils-Göran Larsson. Also on the co-founding team are Paul Thurk, an ARCH managing director who passed away in early 2021, and science chief Gabriel Martinez, whose résumé includes Praxis, Sage, AstraZeneca and Vertex.
The scientific founders come from European institutes, hence the company’s locations in Gothenburg, Sweden, and Waltham, MA. Parrish, whose favorite pretzels are Utz (hard) and mustard (soft), said the company did its research on the history of pretzels, and it turns out there are “many countries in Europe that claim ownership of the pretzel, so it’s very controversial.”
Mitochondria look like pretzels, hence the name, but the company’s logo goes further on the symbolism to include an illustration of 13, representing the number of proteins that mitochondria codes for.
So far, the pretzels are turning out alright.
“In startups, they’re never linear. Your plan never survives the first day,” Parrish said. “While we threw everything against the wall, a lot of it stuck, and we weren’t expecting that to happen.”
Other mitochondrial biotechs in the works include March Therapeutics out of MIT and cell therapy startup Minovia Therapeutics, which is partnered with Astellas.
Pretzel’s suite of financial backers also includes: HealthCap, Cambridge Innovation Capital, Cambridge Enterprise, Angelini Ventures, Google’s GV, Invus, Eir Ventures, GU Ventures and Karolinska Institutet Holding.
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