Korro Bio Reports Over 90% SERPINA1 Editing and 95% Z-AAT Reduction with KRRO-111
Korro Bio added KRRO-111 as a development candidate for alpha-1 antitrypsin deficiency, reporting over 90% in vivo SERPINA1 transcript editing and ~90% functional AAT protein restoration in mouse models. In repeat-dose studies, a 3 mg/kg regimen reduced pathogenic Z-AAT production by ~95% and cleared existing aggregates by 69%.
1. Candidate Selection and Mechanism
Korro Bio selected KRRO-111 as its development candidate for AATD, a GalNAc-conjugated oligonucleotide designed for subcutaneous delivery to hepatocytes. The compound harnesses ADAR-mediated RNA editing to correct the G-to-A SNV in SERPINA1 mRNA, restoring normal alpha-1 antitrypsin production without altering DNA.
2. Preclinical Efficacy Data
In mouse models with the PiZZ genotype, KRRO-111 achieved over 90% SERPINA1 transcript editing, resulting in ~90% functional AAT protein levels. A repeat-dose regimen of 3 mg/kg reduced pathogenic Z-AAT synthesis by ~95% and cleared 69% of existing protein aggregates by day 28, demonstrating potential dual lung and liver benefits.
3. Development Outlook
The company is preparing to advance KRRO-111 into clinical testing alongside its KRRO-121 program for urea cycle disorders. Robust preclinical results support potential best-in-class positioning and the firm remains well-capitalized to report initial clinical data from both programs.