CAMBRIDGE, Mass. — AIRNA said it is presenting new preclinical data on its lead RNA-editing candidate for alpha-1 antitrypsin deficiency and its cardiometabolic research programs at the American Society of Gene and Cell Therapy annual meeting in Boston.
The Cambridge-based biotech company said the data support the potential of its RNA-editing platform to repair disease-causing variants and introduce protective variants associated with human health.
AIRNA’s lead candidate, AIR-001, is being developed for alpha-1 antitrypsin deficiency, or AATD, a genetic disease caused by mutations in the SERPINA1 gene that reduce levels of functional alpha-1 antitrypsin protein. The condition can lead to progressive lung disease and liver injury.
“We are excited to showcase for the first time our robust preclinical data for AIR-001 — now being evaluated in the clinic — as well as new data that illustrate the breadth of AIRNA’s RNA-editing platform,” said Sriram Sathy, Ph.D., Chief Scientific Officer of AIRNA. “From repairing disease-causing variants to introducing protective variants, we believe RNA editing offers a powerful and flexible approach to therapeutic development.”
AIR-001 is a subcutaneously delivered GalNAc oligonucleotide designed to correct the most common disease-causing mutation of AATD, known as PiZ, at the RNA level. The candidate is currently being evaluated in a phase 1 clinical trial.
In a mouse model of AATD, AIRNA said AIR-001 showed potent and precise editing of the PiZ mutation, with no off-target edits observed. The company said liver RNA editing showed dose-dependent effects, with the 10 mg/kg dose achieving 59% editing. That corresponded with more than 40 µM of corrected alpha-1 antitrypsin in serum and 70 µM total AAT.
A longer-term mouse study found that biweekly AIR-001 dosing over 15 weeks led to accumulating levels of corrected and total AAT, which AIRNA said suggests the potential for long-term benefit. The company also reported improvement across lung and liver disease-relevant endpoints, including a more than 30-fold increase in neutrophil elastase inhibition.
In non-human primate studies, AIR-001 demonstrated tolerable and durable liver exposure, supporting the potential for dosing once every eight to 12 weeks in humans, according to the company.
AIRNA also presented preclinical proof-of-concept data from its cardiometabolic portfolio. The company said its RNA-editing approach may be able to introduce protective genetic variants linked to lower cardiovascular disease risk.
In one program targeting the low-density lipoprotein receptor gene, AIRNA developed an RNA-editing oligonucleotide designed to replicate the effect of a protective LDLR variant associated with substantially lower LDL cholesterol. In human hepatocytes, the editor achieved up to 70% editing and a 3.5-fold increase in LDLR expression.
In a humanized mouse model, AIRNA said treatment resulted in a 92% reduction in LDL cholesterol. Combination dosing with alirocumab, an approved anti-PCSK9 antibody, produced greater LDL cholesterol reduction at lower doses than alirocumab alone, supporting potential use as a standalone therapy or alongside existing lipid-lowering treatments.
AIRNA also explored apolipoprotein B, a cardiovascular disease target where previous therapeutic approaches have been limited by liver toxicity. The company said RNA editing to replicate a protective APOB variant achieved 30% editing in vivo, a 21% decrease in ApoB protein and a 17% reduction in LDL cholesterol, without observed liver toxicity.
AIR-001 has received Orphan Drug Designation from the U.S. Food and Drug Administration for the treatment of alpha-1 antitrypsin deficiency and is being evaluated in the phase 1 RepAIR1 clinical trial.
