Korro Bio presents new data for KRRO-110, reported portfolio progress

Korro Bio presented new data for KRRO-110 and reported progress across its RNA editing portfolio at the J.P. Morgan Healthcare Conference on January 9, 2024. Pipeline updates: KRRO-110: As announced on December 7, 2023, Korro selected KRRO-110 as its first development candidate for the potential treatment of AATD, an inherited genetic disorder caused by single nucleotide variants in the SERPINA1 gene. Preclinical data to date for KRRO-110 demonstrated: High specificity with no bystander effects in MZ human primary hepatocytes; Intravenous administration at 2 mg/kg resulted in secretion of ~50microM functional AAT as early as 7 days post-single dose in a human transgenic PiZ mouse model; Increase in AAT protein and the inhibition of elastase activity were sustained through week 9 when dosed every 2 weeks, demonstrating durability in mice; Greater than 40% editing in NHPs utilizing an earlier generation oligonucleotide designed to edit a surrogate SERPINA1 RNA target site; Preclinical development of KRRO-110 is ongoing in preparation for a regulatory filing expected in the second half of 2024, with a potential interim clinical readout in the second half of 2025. Platform Update: Korro’s proprietary RNA editing platform, OPERA, integrates a deep understanding of adenosine deaminase acting on RNA (ADAR) enzymology with expertise in oligonucleotide chemistry, machine learning optimization of oligonucleotides and fit-for-purpose delivery. CHORDs, or Customized High-fidelity Oligonucleotides for RNA Deamination, are single-stranded, anti-sense oligonucleotides designed to have high target efficiency and specificity by leveraging the pillars of OPERA. Creating De Novo Mutation to Alter Protein Function: In addition to repairing pathogenic SNVs, CHORDs can be used to engineer de novo SNVs and change amino acids on proteins to endow them with desired altered properties while still preserving their broader functional capabilities. In preclinical studies, Korro has demonstrated the ability to: Activate a transcription factor in an undisclosed target ; Demonstrated activation of a transcription factor by creating a de novo protein variant resulting in sustained downstream activity in NHPs lasting longer than 21 days, demonstrating potential to preserve transcription factor function; Selectively modulate TDP-43 to reduce protein aggregation ; TDP-43 is a protein associated with ALS, FTD and other neurodegenerative diseases. A single RNA edit to TDP-43 is predicted to lead to the synthesis of a protein variant that does not aggregate, thereby preserving normal function and protecting downstream activity essential for neuronal health; Modulate ion channels to within physiological levels in Nav1.7 ; Nav1.7 is a voltage-gated sodium channel that is essential for pain sensation and electrical signaling in the central nervous system. Korro has demonstrated that site-specific changes are sufficient to decrease the activity of Nav1.7. This approach has the potential to deliver potent analgesic activity without the dose-limiting toxicities that have been observed by sodium channel blockers