CAMBRIDGE, Mass. — October 5, 2026
Korro Bio, Inc. announced that the first cohort of participants has been dosed in the Phase 1/2 ANCHOR clinical trial of KRRO-121, an investigational GalNAc-conjugated RNA-editing oligonucleotide for the treatment of hyperammonemia associated with urea cycle disorders (UCDs) and hepatic encephalopathy (HE). The first cohort of healthy volunteers received a single 2 mg/kg dose as part of the Phase 1 single ascending dose study. Korro expects to begin dosing patients with UCDs in the first half of 2027, with an interim clinical readout anticipated in the second half of 2027.
KRRO-121 Uses RNA Editing to Address Hyperammonemia
KRRO-121 is designed to generate a stabilized, de novo glutamine synthetase (GS) protein to enhance ammonia clearance. The candidate uses Korro’s OPERA® RNA-editing platform to modify targeted native mRNA transcripts rather than permanently altering DNA. By producing a functional synthetic GS protein, KRRO-121 is intended to increase the body’s ability to remove excess ammonia from the bloodstream. The approach is being developed as a potential treatment for UCD patients regardless of their underlying genetic mutation, potentially addressing a broad patient population across different UCD genotypes..
ANCHOR Trial Evaluates Safety and Clinical Activity
The global ANCHOR program consists of two clinical development components evaluating KRRO-121 in healthy volunteers and patients with UCDs. Part 1 includes a Phase 1 single ascending dose study followed by a multiple ascending dose study in up to 50 healthy volunteers, with safety, tolerability and pharmacokinetics as the primary objectives. The single ascending dose portion is expected to enroll up to 30 participants across five cohorts, while the multiple ascending dose portion will evaluate selected doses in up to 20 participants. Part 2 is planned as a Phase 2 multiple-dose study in up to 15 UCD patients across all UCD genotypes, subject to regulatory approval, to evaluate safety, tolerability, pharmacokinetics and preliminary clinical activity.
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Korro Advances Potential Pan-UCD RNA Editing Therapy
Korro is developing KRRO-121 as a potential disease-modifying approach that could provide broader and more convenient control of hyperammonemia. Preclinical studies have supported the potential for KRRO-121 to reduce ammonia excursions, potentially enable greater dietary flexibility, reduce dependence on nitrogen-scavenging therapies and lower the risk of hyperammonemic crises. The candidate is designed for infrequent subcutaneous administration, which could offer an advantage over existing treatments that may require multiple daily doses. Korro is also evaluating the potential application of KRRO-121 in hepatic encephalopathy, where impaired ammonia clearance can contribute to recurrent neurological complications. With clinical dosing now underway and UCD patient dosing expected in 2027, the ANCHOR program represents an important step toward determining whether Korro’s RNA-editing approach can translate its preclinical findings into a broadly applicable treatment for hyperammonemia.
Source: Korro Bio, press release
