A developer of RNA editing therapies whose lead program targets Alpha-1 antitrypsin deficiency (AATD) said today it has closed an oversubscribed $60 million Series A financing, with plans that include advancing the treatment into the clinic next year.
In addition to launching clinical trials assessing the AATD candidate, AIRNA says it will use proceeds from the Series A to build up a pipeline that is envisioned to go beyond rare diseases.
“We were really fortunate in this difficult funding environment to be in a position where we were oversubscribed. We had more interest than we were able to accommodate and had a unique opportunity to really select the investors that we wanted to work with,” president and CEO Kris Elverum told GEN Edge.
He said AIRNA isn’t disclosing how long of a runway the financing will give the company, how large of a pipeline it is hoping to develop, or specific candidates in that pipeline.
However, Elverum did say AIRNA is looking to develop therapies for common disorders in numerous therapeutic areas.
“We’re looking at larger indications with high unmet need, such as cardiovascular disease, metabolic disorders, blood disorders, and others where RNA editing can provide unique therapeutic potential,” Elverum said. “This financing that we’ve completed is, I think, quite a strong validation of not only the superiority of our technology and our data for AATD, but also the broad potential of our platform across a variety of these different indications to really help patients in need, and in multiple different ways.”
Some pipeline candidates will be developed through collaborations with larger partners, he added: “there’s so much we can do with RNA editing yet as a small company, there’s only so much we’re able to do ourselves.”
AIRNA is among several companies focused on developing RNA-edited therapies. Furthest along in the clinic to date is Wave Life Sciences, which expects later this year to release RNA editing proof-of-mechanism data for its own AATD treatment WVE-006, now under study in the Phase Ib/IIa RestorAATion-2 trial (NCT06405633). WVE-006 is a GalNAc-conjugated, subcutaneously delivered RNA editing oligonucleotide for which GlaxoSmithKline (GSK) has an exclusive global license.
Also among RNA-edited therapy developers are
- Korro Bio, which plans to file an application with regulators for a first-in-human study of KRRO-110 in patients with AATD in the second half of this year.
- Shape Therapeutics (ShapeTX), which in May published data showing that its RNAfix editing platform held potential to treat central nervous system (CNS) disorders, achieving up to 92% editing in the non-human primate brain after AAV-based guide RNA (gRNA) delivery, and >95% editing throughout the mouse brain with sustained durability at least 6 months post-dose.
- Ascidian Therapeutics, which in June joined Roche to launch an up-to-$1.8 billion collaboration to discover and develop RNA exon editing therapeutics targeting neurological diseases using Ascidian’s RNA exon editing platform.
“More translatable”
“Our technology is eminently more translatable to delivering a target product profile that is exciting for patients,” Elverum said. “We’ve been able to solve that in vitro to in vivo challenge that so many in the industry have struggled with.”
He cited the AATD program, which he said will combine optimal potency with a safe drug that can be easily administered subcutaneously and infrequently: “That differentiation is really important for patients, but also allows us to move from target to target. I think we understand the biology of RNA editing in a very unique way that allows us to also exploit the full potential of RNA editing as a modality.”
AIRNA develops therapies based on its RESTORE+™ RNA editing platform. RESTORE+ first targets a defined site in the RNA strand, activating changes to composition and functionality of a therapeutically relevant protein. The platform optimizes the chemistry, sequence, and delivery of oligos that precisely engage the RNA at the target site upon delivery into the cell, with the goal of enabling precise, efficient, and safe RNA editing.
Following target engagement, the oligo recruits endogenous adenosine deaminases acting on RNA (ADAR) to make an adenosine-to-inosine (A-to-I) edit at the target site that is read as guanosine (G). The A-to-I edit changes the code in the RNA, enabling the repair of pathogenic point mutations, or inducing therapeutically effective gain or loss-of-function mutations that precisely change protein activity.
“I think the advantage by changing individual letters in the RNA are multi-fold,” Elverum explained. “Number one is, it’s temporary. You can start or stop. You can dose up or down. You give patients and physicians the freedom to continue to make choices about their healthcare, and what medicine’s optimal for them as their lives evolve, and as their health evolves.”
“Importantly, it allows us to go after biology for large indications where the root cause is most often at the RNA and protein level,” he continued. “And that means that we can deliver a drug product that can be preferred by patients earlier in the disease course, but also that can target biology. That’s really fit for purpose for those large indications.”
Pioneering research
RESTORE+ is based on pioneering research by AIRNA’s two academic co-founders, Thorsten Stafforst, PhD, of the University of Tübingen and Jin Billy Li, PhD, of Stanford University. Stafforst’s lab in 2012 published the first paper showing the selective repair of point mutations in messenger RNA (mRNA) through site-selective editing on a specific codon.
Stafforst, Li, and co-founders Paul Vogel and Tobias Merkle were the first to publish peer-reviewed papers showing ADAR-mediated RNA editing and the use of oligonucleotides to recruit endogenous ADAR for targeted RNA editing.
In 2019, Stafforst—the founding member of the Gene and RNA Therapy Center (GRTC) at University Hospital Tübingen—was corresponding author, and the other three co-founders were among eight co-authors of a study demonstrating how an earlier version of the platform, RESTORE (recruiting endogenous ADAR to specific transcripts for oligonucleotide-mediated RNA editing), enabled the engineering of chemically optimized antisense oligonucleotides that recruited endogenous human ADARs to edit endogenous transcripts in a simple and programmable way.
“We successfully applied RESTORE to a panel of standard human cell lines and human primary cells and demonstrated repair of the clinically relevant PiZZ mutation, which causes α1-antitrypsin deficiency, and editing of phosphotyrosine 701 in STAT1, the activity switch of the signaling factor,” the co-authors reported in Nature Biotechnology. “We observed almost no off-target editing, and natural editing homeostasis was not perturbed.”
“That’s when you saw a lot of venture capital firms and companies that knew how to make oligonucleotides get excited about the space and tried to get in it,” Elverum recalled. “Ultimately Thorsten and Billy decided to form their own company, which became AIRNA.”
Emerging from stealth
AIRNA emerged from stealth in September 2023 with $30 million in initial financing from an investor syndicate led by ARCH Venture Partners. The Series A round brings AIRNA to $90 million in total capital raised.
Forbion led the Series A financing, with participation from Ono Venture Investment, Alexandria Venture Investments (the venture arm of Alexandria Real Estate Equities), other undisclosed new investors—as well as AIRNA’s syndicate from its initial financing last year, which included ARCH Venture Partners and ND Capital (formerly NanoDimension).
“This financing is a flagship example of a new investment model, where we were able to bring together the best investors in Europe and in the U.S., with Forbion and ARCH in particular, to work together with a team that’s also being built across continents and across countries to develop the strongest therapeutic options,” Elverum added.
Forbion is headquartered in Naarden, The Netherlands, with a Boston office announced last month and an additional office in Munich, Germany. ARCH has offices in Chicago, Seattle, and San Francisco.
In connection with the financing, AIRNA has appointed Josh Brumm, General Partner at Forbion, to its board. Brumm was formerly President and CEO of Dyne Therapeutics, a Forbion portfolio company working to develop oligonucleotide-based therapies to treat muscle diseases.
Building a trans-Atlantic team is no small concern to AIRNA, which promotes a single, collaborative company culture even as its operations are divided between its home base in Cambridge, MA, and Tübingen, Germany, where the company oversees a research hub. AIRNA won’t disclose the size of its workforce, though Elverum said the company plans to expand it over time.
“We’ll be growing our science team, our translational team, the medical function, legal business functions,” Elverum said. “We’re really growing across multiple areas within the company, both in Cambridge as well as in Germany. And that is really important to us, because we want to have the best team.”
