Korro Bio (KRRO) 44th Annual J.P. Morgan Healthcare Conference summary

Technology and Platform Overview

• Focus on developing transformative medicines for rare and prevalent diseases by activating biological pathways using RNA editing, specifically converting adenosine to inosine in RNA to impact protein structure and function.

• Platform, OPERA, is built on four pillars: understanding ADAR biology, oligonucleotide chemistry, delivery technologies, and machine learning for target identification and design.

• Employs modular delivery platforms, including GalNAc-conjugated systems, to target multiple cell types and leverages genetic insights for predictable outcomes.

• RNA editing enables precise, transient, and modular interventions, allowing for tissue- and cell-type specificity without permanent DNA changes.

• RNA editing enables repair of pathogenic variants and generation of protein variants to modulate or restore function.

Pipeline Highlights and Clinical Progress

• Lead program KRRO-121 targets stabilization of an intracellular liver protein to reduce ammonia in multiple indications, with regulatory filing and clinical entry expected in the second half of the year and a workshop on Jan. 27, 2026.

• KRRO-121 aims to treat all urea cycle disorders and hepatic encephalopathy, addressing large unmet needs with a once-monthly subcutaneous therapy and a market opportunity estimated at $1.5B–$2B+ in the US and EU/UK.

• Next-generation Alpha-1 (AATD) program shows nearly 100% editing in animal models using GalNAc delivery, with development candidate nomination anticipated in the first half of 2026.

• Third GalNAc-conjugated liver asset development candidate expected in the second half of 2026.

• Terminated Korro 110 after suboptimal clinical data and leveraged learnings to improve subsequent programs, shifting from lipid nanoparticle to Gal-conjugate delivery.

Scientific Advances and Differentiation

• Demonstrated ability to create highly selective, isoform-specific activators (e.g., AMPK gamma-1) for metabolic diseases, overcoming toxicity seen with systemic small molecules and showing improved liver function and reduced body weight in obese mice.

• ALS program restores TDP-43 function by preventing aggregation and mislocalization, achieving effects not possible with other modalities and showing reduced mis-splicing and protein mis-localization.

• RNA editing offers high specificity with minimal off-target effects, supported by preclinical and clinical data.

• Platform enables rapid development cycles, reducing time to candidate nomination for new targets.