ARCH-backed startup AIRNA launches with $30M for RNA editing therapies

The race to develop new therapies that precisely edit short-lived RNA molecules instead of making irreversible changes to DNA is heating up. A new entrant to the growing field emerged from stealth Tuesday morning with a $30 million initial financing round led by ARCH Venture Partners to make RNA editing therapies for both rare and common diseases.

Thorsten Stafforst

The startup, called AIRNA, was co-founded in 2021 by Thorsten Stafforst — a University of Tübingen biochemist whose work over the past decade helped spark interest in RNA editing therapies — and Jin Billy Li, a Stanford University biologist who has studied the enzymes that power RNA editing in nature since 2006.

“There’s a difference between the people who read the seminal papers in this space versus the people who wrote the papers,” CEO and president Kris Elverum told Endpoints News in an interview. “And I feel very fortunate that we have the people who wrote the seminal papers.”

The therapies alter a single letter in messenger RNA to correct genetic disease or introduce a protective mutation. The change is temporary, and the medicines should be redosable, Elverum said. “It’s a modality that will make the benefits of editing accessible to everyone, and I think preferred by patients as an approach to address their disease,” he added.

Kris Elverum

Yet several other companies have a head start, including Wave Life Sciences, which recently asked regulators for permission to begin the first-ever clinical trial of an RNA editing therapy. That treatment is designed to fix a mutation that causes alpha-1 antitrypsin deficiency, or AATD, where misfolded proteins lead to damage in the lungs and liver. RNA editing company Korro Bio plans to begin a clinical trial for its own AATD treatment in the second half of 2024.

AIRNA has also chosen AATD as its lead program since the disease is caused by a genetic typo that RNA editing can easily reverse. Elverum wouldn’t say how far away the company is from testing the drug in the clinic, only that he believes they will have a “best in class” program, although he doesn’t have plans to disclose the preclinical data.

ND Capital, Fast Track Initiative, Novalis and Codon Capital chipped into the initial financing, which Elverum said was not being branded as either a seed or Series A round. And Rodger Novak, the co-founder and former chairman of CRISPR Therapeutics, joined AIRNA as its board chair.

‘Endless opportunities’ for RNA editing

The startup’s therapies work by controlling a human enzyme called ADAR, which converts an adenosine base in mRNA into an unusual base called inosine. The process, which occurs naturally in human cells, is called A-to-I editing — the inspiration for the startup’s portmanteau of “AI” and “RNA.”

Because the cell’s protein-making machinery interprets inosine as the more common guanosine, RNA editing is well-suited to treat genetic diseases caused by an adenosine typo where a guanosine should be. AATD is one of those diseases.

Stafforst began developing tools to control RNA editing in 2011, initially relying on methods that chemically linked ADAR to an RNA molecule that directed the enzyme to its target. Although the approach attracted some investors, Stafforst felt the technology wasn’t ready for prime time. “It was simply too early for the field and for my career,” he told Endpoints.

That changed in 2019 after Stafforst and Li published a study in Nature Biotechnology showing that chemically modified oligonucleotides on their own — something easier to develop as a drug — could recruit ADAR to make specific edits. The work led the two scientists, along with co-authors Paul Vogel and Tobias Merkle, to found AIRNA.

“For us, it was very good that there were competing companies arising and that there was already huge interest from investors,” Stafforst said.

Correcting G-to-A mutations is a “no-brainer” for RNA editing, but only the beginning, Stafforst said. “There are so many more things you can do. You can think about modulating protein function, modulating metabolism and modulating signaling cues. I think there are endless opportunities,” he said.

Stafforst explained that by introducing mutations, the company could change key amino acids in proteins to add or eliminate their ability to perform specific functions. “We have played around with this quite a lot,” he said. For example, RNA editing could be used to change a protein’s ability to be phosphorylated or alter its ability to bind to other proteins or natural ligands, he added.

Elverum said that AIRNA has “identified many high-value targets that no one else is pursuing.” He wouldn’t disclose details or provide examples, but he did say there will be room for multiple winners in the RNA editing race.

“The RNA editing field is going to be enormous,” Elverum said. “I think there are multiple RNA editing companies that are going to help a lot of patients and be wildly successful.”

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