Korro Reports Best-in-Class Preclinical Data for KRRO-111 Demonstrating Potential to Benefit Lung and Liver Manifestations of Alpha-1 Antitrypsin Deficiency

Mouse studies showed restoration of functional AAT alongside reduced liver levels of the pathogenic protein.

Rhea-AI Summary

Korro Bio (KRRO) reported preclinical results for KRRO-111, its RNA-editing candidate for alpha-1 antitrypsin deficiency affecting the lungs and liver.

In repeat-dose NSG-PiZ mouse studies, editing of SERPINA1 messenger RNA reached 96%; functional M-AAT comprised 93% of circulating AAT. Total AAT reached 172 μM, approximately six-fold versus vehicle, at Day 57. In a separate immunocompetent C57BL/6-PiZ mouse study, whole-liver levels of pathogenic Z-AAT fell 95% versus vehicle at Day 57. Single-dose studies produced up to 91% editing, with M-AAT accounting for up to 88% of circulating AAT; both responses remained detectable through at least Day 42.

Korro expects a regulatory submission in the first half of 2027 and aims to advance KRRO-111 into the clinic in that period. These findings concern preclinical studies, not patient outcomes.

Positive

• Minor pointRepeat-dose NSG-PiZ mouse studies achieved 96% SERPINA1 RNA editing.
• Minor pointFunctional M-AAT comprised 93% of total circulating AAT in repeat-dose NSG-PiZ mouse studies.
• Minor pointTotal AAT reached 172 μM, approximately six-fold versus vehicle, at Day 57 in NSG-PiZ mice.
• Minor pointWhole-liver pathogenic Z-AAT declined 95% versus vehicle at Day 57 in immunocompetent C57BL/6-PiZ mice.
• Minor pointSingle-dose C57BL/6-PiZ studies achieved up to 91% editing, detectable through at least Day 42.

3 minor points

• Minor pointSingle-dose C57BL/6-PiZ studies produced M-AAT at up to 88% of circulating AAT, detectable through at least Day 42.
• Minor pointMouse and human liver-cell studies achieved up to 98% editing, with approximately 1 nM half-maximal effective concentration.
• Minor point. Forward-looking: it has not happened yet and may not happen.Korro expects regulatory submission in the first half of 2027 and targets clinical advancement in that period.

Negative

• None.

Key Figures

EC50: ~1 nM RNA editing: Up to 98% SERPINA1 mRNA editing: 96% +5 more

EC50

~1 nM

KRRO-111 RNA editing activity

RNA editing

Up to 98%

Mouse and human hepatocytes

SERPINA1 mRNA editing

96%

NSG-PiZ mice, Day 57

M-AAT share of circulating AAT

93%

NSG-PiZ mice, Day 57

Total AAT concentration

172 μM (~6-fold vs. vehicle)

NSG-PiZ mice, Day 57

Liver Z-AAT reduction

95%

Relative to vehicle control in C57BL/6-PiZ mice, Day 57

Response detectability

Through at least Day 42 post-dose

Single-dose C57BL/6-PiZ mouse studies

Regulatory submission

First half of 2027

Expected timing for KRRO-111

Key Terms

alpha-1 antitrypsin deficiency, lc-ms/ms

2 terms

alpha-1 antitrypsin deficiency medical

"for the potential treatment of alpha-1 antitrypsin deficiency (AATD)"

A genetic condition in which the body makes too little of a protective protein called alpha‑1 antitrypsin, leaving lungs and sometimes the liver vulnerable to damage; imagine a car missing some brake pads so wear and tear accelerates. It matters to investors because the condition defines a specific patient population, shapes demand for diagnostics and therapies, and concentrates regulatory, clinical trial and reimbursement risks and opportunities for companies developing treatments.

lc-ms/ms technical

"as measured by liquid chromatography tandem mass spectrometry (LC-MS/MS)"

LC‑MS/MS is a laboratory technique that first separates a mixture of chemicals in a liquid, then identifies and measures each component with very high sensitivity—think of sorting mixed mail and then scanning barcodes to know exactly what’s inside. It matters to investors because it produces precise, reliable data used in drug development, safety testing, diagnostics and product quality control, and those results influence regulatory approvals, market access and commercial claims that can affect a company’s value.

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• Repeat dose mouse studies achieved >95% SERPINA1 mRNA editing, sustained restoration of circulating functional M-AAT and increased total AAT by ~6-fold

• KRRO-111 reduced pathogenic hepatic Z-AAT by up to 95%, highlighting its potential to reduce toxic protein accumulation in the liver

• Best-in-class preclinical profile supports KRRO-111’s potential to address both liver and lung manifestations of AATD; regulatory submission expected in the first half of 2027

CAMBRIDGE, Mass., Oct. 22, 2026 (GLOBE NEWSWIRE) -- 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.

Korro intends to use its Investor Relations website, LinkedIn, and X (Twitter) as means of disclosing material nonpublic information and for complying with its disclosure obligations under Regulation FD. Accordingly, investors should monitor Korro’s Investor Relations website and follow @KorroBio on LinkedIn, and X (Twitter), in addition to following Korro’s press releases, SEC filings, public conference calls, presentations, and webcasts.

Forward-Looking Statements

Certain statements in this press release may constitute “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements include, but are not limited to, express or implied statements regarding expectations, hopes, beliefs, intentions or strategies of Korro regarding the future including, without limitation, express or implied statements regarding: the best-in-class and best-in-disease potential of, and market opportunity for, KRRO-111 as a treatment for AATD, including its potential to address both the lung and liver manifestations of AATD and to become a transformative therapy, and its potential as a redosable subcutaneous therapy; the extent to which preclinical results for KRRO-111, including M-AAT restoration and reduction and clearance of Z-AAT observed in mouse models, will be predictive of results in humans; KRRO-111’s ability to achieve the functional equivalent of a DNA modification without altering the genome; the ongoing GLP toxicology evaluation of KRRO-111; the timing of a regulatory submission for KRRO-111, including the expected submission in the first half of 2027; and the advancement of KRRO-111 into clinical development and reaching and reporting clinical milestones for KRRO-111; among others. In addition, any statements that refer to projections, forecasts, or other characterizations of future events or circumstances, including any underlying assumptions, are forward-looking statements. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “might,” “plan,” “possible,” “potential,” “predict,” “project,” “should,” “strive,” “would,” “aim,” “target,” “commit,” and similar expressions may identify forward-looking statements, but the absence of these words does not mean that a statement is not forward-looking. Forward-looking statements are based on current expectations and assumptions that, while considered reasonable by Korro and its management, are inherently uncertain. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. Factors that may cause actual results to differ materially from current expectations include, but are not limited to, various factors beyond management’s control including risks associated with pre-clinical studies and conducting clinical trials; risks associated with validating in clinical trials observations from pre-clinical studies, including the risk that results of pre-clinical studies, including in animal models, may not be predictive of results in humans; competition from other companies and therapies, and the absence of head-to-head comparisons supporting any best-in-class potential; risks associated with collaborating with third parties; changes in policies, staffing or priorities at the FDA or other regulatory authorities; other risks associated with obtaining regulatory approvals and protecting intellectual property; as well as risks associated with general economic conditions; and other risks and uncertainties indicated from time to time in Korro’s filings with the Securities and Exchange Commission (SEC), including under the caption “Risk Factors” in Korro’s most recent Quarterly Report on Form 10-Q or Annual Report on Form 10-K, as such may be amended or supplemented by its other filings with the SEC. Nothing in this press release should be regarded as a representation by any person that the forward-looking statements set forth herein will be achieved or that any of the contemplated results of such forward-looking statements will be achieved. You should not place undue reliance on forward-looking statements in this press release, which speak only as of the date they are made and are qualified in their entirety by reference to the cautionary statements herein. Except as required by law, Korro does not undertake or accept any duty to release publicly any updates or revisions to any forward-looking statements to reflect any change in its expectations or in the events, conditions or circumstances on which any such statement is based. This press release does not purport to summarize all of the conditions, risks and other attributes of an investment in Korro.

Korro Bio Contact Information

Investor & Media Contact
Malini Chatterjee, PhD
Blueprint Life Science Group
mchatterjee@bplifescience.com or ir@korrobio.com
917.330.4269

FAQ

AI-generated questions and answers. How Rhea-AI works. Not financial advice.

What did Korro's KRRO-111 preclinical studies show for alpha-1 antitrypsin deficiency?

KRRO-111 restored functional M-AAT in mouse studies and reduced pathogenic liver Z-AAT. Repeat-dose NSG-PiZ studies reached 96% RNA editing, while a separate immunocompetent C57BL/6-PiZ mouse study showed a 95% reduction in whole-liver Z-AAT versus vehicle at Day 57.

When does Korro expect to submit KRRO-111 to regulators?

Korro expects a regulatory submission for KRRO-111 in the first half of 2027 and aims to advance the candidate into the clinic during that period.