CAMBRIDGE, Mass.— Korro Bio, Inc. (Korro) (Nasdaq: KRRO), a clinical-stage biopharmaceutical company leveraging its novel oligonucleotide promoted editing of RNA (OPERA®) platform to develop a new class of genetic medicines for rare and highly prevalent diseases, today announced preclinical results for its pipeline program KRRO-111 for the potential treatment of alpha-1 antitrypsin deficiency (AATD) delivered subcutaneously. The results highlight KRRO-111’s potential best-in-class profile and its ability to address both the lung and liver manifestations of AATD through a differentiated RNA editing approach.
“In these preclinical studies, KRRO-111 restored functional M-AAT while reducing the toxic Z-AAT that drives liver injury,” said Loïc Vincent, PhD, Chief Scientific Officer of Korro. “That dual profile, with a redosable subcutaneous drug presentation, is what we believe a next-generation AATD therapy needs to support all AATD patients.”
KRRO-111 is a proprietary GalNAc-conjugated RNA-editing oligonucleotide administered subcutaneously and selectively taken up by liver cells. Once inside the liver cells KRRO-111 harnesses endogenous Adenosine Deaminase Acting on RNA (ADAR) enzymes to correct the pathogenic SERPINA1 transcript, enabling production of M-AAT, while reducing synthesis of mutant Z-AAT.
KRRO-111 exhibited potent RNA editing activity (EC50 ~1 nM) achieving up to 98% editing in mouse and human hepatocytes. In single-dose studies in the C57BL/6-PiZ mouse model, KRRO-111 produced up to 91% SERPINA1 editing, with M-AAT accounting for up to 88% of total circulating AAT, and both responses remaining detectable through at least Day 42 post-dose.
In repeat-dose studies, KRRO-111 produced sustained RNA editing and restoration of circulating M-AAT across multiple subcutaneous dosing regimens. In NSG-PiZ mice, SERPINA1 mRNA editing reached 96%, with M-AAT comprising 93% of total circulating AAT and total AAT concentrations reaching 172 μM (~6-fold vs. vehicle) at Day 57. In immunocompetent C57BL/6-PiZ mice, KRRO-111 reduced whole liver Z-AAT levels by 95% relative to vehicle control, as measured by liquid chromatography tandem mass spectrometry (LC-MS/MS) at Day 57.
“People living with AATD face both lung and liver disease. Augmentation therapy addresses only part of that burden while there is no approved therapy for the liver disease,” said Ram Aiyar, PhD, MBA, Chief Executive Officer and President of Korro. “Based on the strength and consistency of these data, we believe KRRO-111 has the potential to become a transformative therapy for both the lung and liver manifestations of AATD, and we look forward to advancing it into the clinic in the first half of 2027.”
Regulatory submission for KRRO-111 is expected in the first half of 2027.
About Alpha-1 Antitrypsin Deficiency (AATD)
AATD is a genetic disorder most commonly caused by a single missense mutation (G-to-A) in the SERPINA1 gene. Affected adults experience pulmonary emphysema and/or hepatic cirrhosis, as well as end organ manifestations. Greater than 95% of severe clinical cases of AATD are homozygous for the PiZ mutation (known as the PiZZ genotype). There are an estimated 3.4 million individuals with deficiency allele combinations worldwide. The only current FDA-approved treatment for AATD is augmentation therapy, a once-weekly infusion of pooled human plasma-derived AAT protein, which remains inadequate to address the lung and liver manifestations of AATD.
About Korro
Korro is a clinical-stage biopharmaceutical company leveraging a novel oligonucleotide promoted editing of RNA (OPERA®) platform to develop a new class of genetic medicines for rare and highly prevalent diseases. OPERA provides precise, tissue-directed delivery of RNA-editing oligonucleotides (REOs) that modify the targeted native mRNA transcript to repair or form a de novo protein with enhanced functionality. The platform combines a suite of capabilities consisting of sophisticated knowledge of transcription biology through ADAR proteins (Adenosine Deaminases Acting on RNA), machine learning optimization of REOs, linker chemistry expertise, along with use of a highly targeted tissue-specific delivery methodology. As such, the OPERA platform has enabled Korro to generate and advance a portfolio of differentiated programs that are designed to harness the body’s natural RNA editing process, providing precise yet transient single base edits to produce therapeutic proteins with augmented activity versus its endogenous counterpart. By editing RNA instead of DNA, Korro is expanding the reach of genetic medicines by delivering additional precision and tunability, which has the potential for increased specificity and improved long-term tolerability. Using an REO-based approach, Korro expects to bring its medicines to patients by leveraging its proprietary OPERA platform with precedented delivery modalities, including N-acetylgalactosamine (GalNAc) conjugated for delivery for subcutaneous administration, manufacturing know-how and established regulatory pathways of approved oligonucleotide medicines. Korro is based in Cambridge, Massachusetts. For more information, visit korrobio.com.
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