RNA editing therapy developer AIRNA has closed on an oversubscribed $155 million Series B financing it said will help it advance its lead program targeting Alpha-1 antitrypsin deficiency (AATD) into a Phase I/II trial this year.
The financing comes less than a year after AIRNA completed a $90 million Series A, of which $60 million was raised just last summer, and at a time when many other startups have struggled to raise venture capital. While president and CEO Kris Elverum said he can’t speak to the broader challenges of early-stage companies pursuing capital, he told GEN Edge that AIRNA’s success with investors reflected their alignment with the company’s three-prong approach to RNA drug development.
“The first is that RNA editing is clearly going to be a breakthrough modality that will deliver multiple medicines to help patients,” Elverum said. “We’re using multiple proven components from other [RNA] modalities—in particular siRNA—to enable optimal potency at lower doses with safe, infrequent, subcutaneous administration.”
The second, he continued, is AIRNA’s effort to develop a best-in-class AATD treatment that will deliver optimal potency at lower doses with safe, infrequent, subcutaneous administration. The third, Elverum added, is AIRNA’s commitment to building a top-tier pipeline.
“AIRNA stands alone in pursuing the introduction of healthy variants to address common diseases with RNA editing. And we’re really excited about the future for what we were going to be able to do across multiple different diseases to help people,” Elverum said.
AIR-001 is designed to restore functional alpha-1 antitrypsin (M-AAT) protein production by precisely repairing the SERPINA1 mutation (PiZ) to address the underlying cause of both lung and liver disease. According to AIRNA, AIR-001 offers potent and durable M-AAT production, convenient, subcutaneous dosing, and well-tolerated safety.
Growing field targets AATD
By focusing on AATD, AIRNA joins a growing field of drug developers targeting the genetic condition. Furthest along is Wave Life Sciences, whose AATD candidate WVE-006 succeeded last October in the first-ever clinical demonstration of RNA editing in humans by achieving positive proof-of-mechanism in an early-phase clinical trial.
Later this year, Wave expects to present additional data from its Phase Ib/IIa RestorAATion-2 trial (NCT06405633) assessing the effect of multiple doses and a higher dose level of WVE-006, on the production of healthy, wild-type, M-AAT protein, and potentially the effect of extended dose intervals. In March, Wave said multi-dosing of patients was ongoing in the trial’s 200 mg cohort, while a second single dose cohort of 400 mg has been launched.
Also pursuing an AATD therapy is Beam Therapeutics, which won FDA clearance for its investigational new drug (IND) application to expand into the United States its ongoing Phase I/II trial (NCT06389877) of BEAM-302, an in vivo liver-targeting lipid-nanoparticle (LNP) formulation of base editing reagents. BEAM-302 is designed to treat AATD by correcting the disease-causing PiZ mutation.
Earlier in March, Beam announced positive initial safety and efficacy data from the trial: a single infusion of BEAM-302 led to rapid, durable, and dose-dependent increases in total AAT across all three dosages studied (20 mg, 40 mg, and 60 mg), as well as new production of corrected protein (M-AAT) and decreases in mutant AAT (Z-AAT). At the high 60 mg dosage, total AAT at day 28 nearly tripled from 4.4 to 12.4 µM, above the 11 µM protective threshold. Beam said the data established clinical proof-of-concept for BEAM-302 as a potential treatment for AATD, as well as for in vivo base editing.
On March 18, Prime Medicine unveiled a preclinical prime editing program designed to treat AATD by using a universal liver lipid nanoparticle (LNP) to edit the PiZ mutation (also known as Pi*Z or E342K) in SERPINA1. Prime said LNP delivery of its Prime Editors showed up to 72% precise correction of the SERPINA1 gene in the hepatocytes of fully humanized mice, restoring over 95% of serum AAT to the corrected isoform, with healthy M-AAT protein in the serum at levels “well above” 20 µM.
A developer of CRISPR-based gene editing therapies, Intellia Therapeutics, ended development in January of its AATD candidate NTLA-3001 as part of a cost-cutting restructuring that included the planned elimination of 27% of its workforce during 2025. That would translate to approximately 110 jobs, based on the workforce total of 403 full-time employees as of February 14 disclosed by Intellia in its Form 10-K annual report.
Functional cure
“I think it’s more important to be best for patients than it is to be first in patients, and the unique opportunity that we have for patients with AATD is to bring them a functional cure that is a very potent repair of the mutation that’s causing their disease,” Elverum said.
“That repair allows for high levels of M-AAT protein to be produced, which is what’s really important for lung function, but to do so at low doses that can be safe and infrequently administered subcutaneously and allow patients to maintain control and freedom over their healthcare choices over the long term,” he added.
AIRNA’s AIR-001 leads a pipeline about which the company has not disclosed many details. Elverum said AIRNA’s therapeutic areas of interest include cardiometabolic disease, where its sole disclosed program entails introducing an as-yet undisclosed beneficial variant in vivo. It’s a similar mechanism to a program in AIRNA’s revealed pipeline for an undisclosed therapeutic area.
Elverum won’t say whether AIRNA’s focus on cardiometabolic disorders will include developing alternatives to glucagon-like peptide 1 (GLP-1) therapies. GLP-1s indicated for obesity and diabetes have grown into blockbuster drugs generating billions of dollars in sales for leading companies Novo Nordisk and Eli Lilly—but which have been linked in studies to side effects ranging from sagging facial skin (“Ozempic face”) to loss of muscle mass.
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.
Growth plan
With operations divided between its home base in Cambridge, MA, and Tübingen, Germany, where the company oversees a research hub, AIRNA foresees growth to its staff of over 50 people this year.
“Our growth is really going to be focused on that next stage of our development as we are bringing our medicines to patients. You can think about the medical function, the manufacturing function, and the like. That is going to be key for us as we move forward,” Elverum said.
The Series B round brings AIRNA to $245 million in total capital raised, and comes less than a year after AIRNA closed on $60 million in financing that was also oversubscribed—and brought the value of the company’s Series A to $90 million. AIRNA emerged from stealth in September 2023 with its first $30 million in initial financing from an investor syndicate led by ARCH Venture Partners.
Venrock Healthcare Capital Partners led the Series B financing, with Forbion Growth serving as co-leader. Participants in the Series B included RTW Investments, Nextech Invest, ARCH Venture Partners, Forbion Ventures, ND Capital, and other undisclosed new and existing investors.
In connection with the latest financing, Melissa McCracken, PhD, a partner at Nextech Invest, has been appointed to AIRNA’s board.
“AIRNA’s innovative approach to RNA editing has the distinctive potential to improve health across large populations by introducing healthy genetic variants for many conditions,” stated Dirk Kersten, managing partner at Forbion. “We are excited to support the expansion of AIRNA’s pipeline of life-changing medicines and the advancement AIR-001 into the clinic.”