Korro Bio Highlights Data for its Lead Program in Alpha-1 Antitrypsin Deficiency (AATD) and Progress Across its RNA Editing Portfolio - Seite 2

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.

• Developed proprietary oligonucleotide chemistry using structural biology insights that enhances in vivo potency and durability of CHORDs
• Computational efficiency enables rapid iteration of CHORDs across targets
• Using CHORDs, Korro achieved greater than 50% editing in vivo utilizing both a ligand-based GalNAc conjugate and an LNP-based delivery approach
  

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 Na_v1.7
  • Na_v1.7 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 Na_v1.7. This approach has the potential to deliver potent analgesic activity without the dose-limiting toxicities that have been observed by sodium channel blockers

J.P. Morgan Healthcare Conference Presentation