AIRNA Secures $60M for Lead RNA-Editing Therapy Clinical Trials

AIRNA, a burgeoning player in the arena of nucleic acid editing technologies, has recently secured an additional $60 million in funding, elevating its series A total to $90 million. This financial boost will facilitate the clinical development of its pioneering RNA-editing therapeutic aimed at treating alpha-1 antitrypsin deficiency (AATD). This funding influx follows AIRNA's initial emergence from stealth mode less than a year ago with $30 million from ARCH Venture Partners. The latest round saw contributions from existing investor ND Capital and new backers including Forbion, Ono Venture Investment, and Alexandria Venture Investments.

CEO Kris Elverum expressed that the new funds will not only support the advancement of their AATD therapy but will also allow for the expansion of AIRNA’s pipeline. “We’ve discovered numerous therapeutic opportunities with our approach beyond AATD,” Elverum stated. “It’s our responsibility to advance these promising scientific developments into patient treatments.”

AIRNA’s innovative RESTORE+ platform focuses on using oligonucleotides to recruit endogenous ADAR enzymes for precise RNA edits. The ADAR system operates by binding an enzyme to double-stranded RNA, converting adenosine (A) to inosine (I), which the cell's translational machinery interprets as guanosine (G). Initially discovered in the 1980s, ADAR enzymes weren’t considered viable for therapeutic or commercial purposes until 2019. This shift occurred when Thorsten Stafforst's lab at the University of Tübingen demonstrated that oligonucleotides could effectively engage the enzymes without necessitating a fusion system with guide RNAs. Stafforst, along with Jin Billy Li from Stanford University, are scientific co-founders of AIRNA.

Since these discoveries, RNA editing technology has gained significant traction, potentially surpassing DNA-editing mechanisms like CRISPR due to its flexibility and reduced risk of causing permanent DNA changes. The RNA editing sphere has seen at least nine biotech startups developing ADAR-based platforms, with major pharmaceutical companies like Eli Lilly, Roche, and GSK investing billions into the technology.

Elverum likens RNA editing to a software update, as opposed to the more permanent hardware changes associated with DNA editing. “RNA editing is temporary and modifiable,” he explained. “We can adjust dosages as needed, and it’s administered safely.”

ADAR offers unique advantages over DNA editing by not only repairing genetic mutations but also potentially introducing protective variants, enhancing gene functions, and preventing detrimental protein interactions. This versatility opens up therapeutic possibilities for a wider range of diseases, including cardiovascular, metabolic, and hematologic disorders. “Many large-scale health issues are rooted in RNA and protein biology,” Elverum noted. “RNA editing allows us to target areas unreachable by other treatment modalities, which is incredibly exciting for its long-term potential.”

Initially, AIRNA aims to demonstrate proof-of-concept for its technology by focusing on AATD, a rare lung and liver condition caused by a G to A mutation in the SERPINA1 gene, which inhibits the production of alpha-1 antitrypsin protein. AIRNA's product, designed for subcutaneous administration, promises best-in-class potency and safety.

Another biotech, Wave Life Sciences, has also embarked on clinical testing for an ADAR-editing therapy in AATD, launching a Phase Ib/IIa study of its WVE-006 program in June. They anticipate proof-of-mechanism data by the end of the year, marking a significant step forward in the RNA-editing therapeutic landscape.