Korro Bio, Inc. (Nasdaq: KRRO) announced on October 22, 2026, preclinical results for its development candidate KRRO-111, intended for the treatment of Alpha-1 Antitrypsin Deficiency (AATD). The company filed an -K with the SEC to incorporate a press release detailing the findings.
KRRO-111 is a proprietary GalNAc-conjugated RNA-editing oligonucleotide administered subcutaneously. The treatment is designed to be selectively taken up by liver cells, where it uses endogenous Adenosine Deaminase Acting on RNA (ADAR) enzymes to correct the pathogenic SERPINA1 transcript. This process aims to enable the production of functional M-AAT while reducing the synthesis of mutant Z-AAT.
According to the filing, KRRO-111 demonstrated potent RNA editing activity with an EC50 of approximately 1 nM. In single-dose studies using the C57BL/6-PiZ mouse model, the candidate achieved up to 91% SERPINA1 editing, with M-AAT accounting for up to 88% of total circulating AAT. These responses remained detectable through at least Day 42 post-dose.
In repeat-dose studies, KRRO-111 produced sustained effects. In NSG-PiZ mice, SERPINA1 mRNA editing reached 96%, with M-AAT comprising 93% of total circulating AAT. Total AAT concentrations were measured at 172 μM, representing approximately a 6-fold increase compared to vehicle controls. Additionally, in immunocompetent C57BL/6-PiZ mice, KRRO-111 reduced whole liver Z-AAT levels by 95% relative to vehicle controls, as measured by liquid chromatography tandem mass spectrometry (LC-MS/MS) at Day 57.
The company stated that the data supports a potential best-in-class preclinical profile for KRRO-111, highlighting its ability to address both lung and liver manifestations of AATD. Korro indicated that a regulatory submission for KRRO-111 is expected in the first half of 2027.
