ASGCT 2026: GalNAc-conjugated RNA editing oligonucleotides achieve high potency in AATD models

Published: 2026-05-15 16:47:32 ET KRRO

Published on 05/15/2026 at 04:47 pm EDT

May 15th, 2026

Tyson Moyer

Our Vision

Activating Biological Pathways

Editing RNA

Without permanently modifying DNA

Modular Delivery

Potential to deliver to multiple cell types

Learning from Genetics

To support predictable biological impact

RNA Editing: Transiently Affecting an A-to-I Edit on RNA Using an Oligonucleotide

Non-viral intracellular delivery of Korro oligo designed to edit a specific adenosine on the target RNA

Harnessing an endogenous enzyme, ADAR, expressed in all human cells for a highly specific edit

Oligo-RNA duplex recruits adenosine

deaminase acting on RNA (ADAR)

ADAR catalyzes

deamination: 'A' to 'I' edit

mRNA translated to

protein with 'I' read as 'G'

DNA with disease-causing mutation

ADAR

Target RNA

ADAR

Adenosine Inosine

Resultant therapeutic protein

Pipeline With Potential High-Value Programs and Anticipated Milestones

CONCEPT

PROGRAM /

INDICATION

DELIVERY

DISCOVERY

PRECLINICAL

DEVELOPMENT

PHASE 1

PHASE 2

PHASE 3

Stabilize Protein

KRRO-121

Hyperammonemia

GalNAc (SC)

Reg filing in 2H 2026

Repair Pathogenic Variant AATD

GalNAc (SC)

AAT

DC in 2Q 2026

Allosteric Activator

Longevity (Liver)

GalNAc (SC)

AMPK1

Overcome LoF and GoF 1

Amyotrophic

lateral sclerosis (ALS)

Intrathecal (IT)

TDP43

Protein repair

De Novo protein creation

1De Novo protein prevents toxic gain-of-function (GoF) with TDP43 aggregation, and continue downstream signaling by overcoming toxic loss-of-function (LOF)

GS = Glutamine Synthetase; AAT = Alpha-1 antitrypsin; AATD = AAT deficiency; AMPK 1 = Regulatory subunit of AMP-activated protein kinase; TDP43 = TAR DNA-binding protein 43; DC = Development Candidate

Healthy Genotype (MM)

M-AAT

M-AAT is secreted from the liver and transported to the lungs, protecting against inflammatory damage

AATD: An Autosomal Recessive Disorder Leading to Liver and Lung Pathology

AATD

Genotype (ZZ)

Z-AAT aggregates in the liver, leading to:

Z-AAT

•

Liver damage from Z-AAT aggregates

Low circulating AAT, causing lung damage

>200k Pi*ZZ individuals in the US + EU

Source: Strnad et al., NEJM (2020); de Serres et al., Chest (2002)

Current Standard of Care Approved Based on Lower Limit of MZ Phenotype

Serum Ranges Across AAT Genotypes

The current standard of care is weekly

intravenous AAT augmentation therapy

50 MM

Serum AAT levels (μM)

= Median AAT for genotype

11 µM

(60 mg/kg/week)

Augmentation therapy targets serum AAT levels > 11 µM ¹ to slow the progression of lung disease and does not address liver damage

Theoretical protective

Odds Ratio MM

COPD 1.0

1.0

8.8

Cirrhosis 1.0

1.5

7.8

0 threshold

Improved outcomes may be attainable by targeting higher total AAT levels

1. 11 µM T-AAT represents the lower bound of the 95% CI of T-AAT in MZ patients Note: COPD = Chronic obstructive pulmonary disease

Source: Nakanishi T. et al. Eur Respir J. (2020); The undiagnosed disease burden associated with alpha-1 antitrypsin deficiency genotypes

AATD-GalNAc Program Has Potential to Impact AATD Patients

Correct AAT protein in a transient, titratable approach

GalNAc

Prevent lung damage via increased circulating M-AAT

GalNAc-conjugated oligonucleotides administered subcutaneously designed to:

Prevent liver damage via decreased Z-AAT aggregates

Restore normal physiology response

to protect against lung inflammation

OPERA Platform Identifies Top-Performing RNA Editing Oligonucleotides Targeting AATD

Innovation in chemistry at the triplet and outside triplet region improves potency and stability

(

PiZ Mouse Hepatocytes

Oligo 1

Here we are presenting the data from one of our leads (Oligo 1)

Note: Editing is measured after 48-hour incubation of PiZ mouse primary hepatocytes with GalNAc-conjugated oligonucleotides (without lipofectamine).

Single Injection Dose-Response Achieves >70% Editing In Vivo C57BL/6 PiZ

GalNAc

Day 0 4

Varying dose levels

% M-AAT Protein

SERPINA1 RNA Editing

Endpoints

measured

Oligo 1

Note: Single subcutaneous dose administered at varying dose levels, from 1 mg/kg to 30 mg/kg; editing efficiencies are measured on day 4. Editing is measured by NGS; protein levels are measured by LC/MS and proportion of M-AAT was calculated from the sum of M-AAT and Z-AAT detected in circulation.

Durable M-AAT Correction Following Single Injection at Low Dose In Vivo C57BL/6 PiZ

% M-AAT Protein

GalNAc

Peak RNA editing: 35% on day 7

Time (day)

Single 3 mg/kg Injection Drives Durable M-AAT Correction In Vivo

Note: Single, subcutaneous dose at 3 mg/kg; editing efficiency is measured by NGS; protein levels measured by LC/MS and proportion of M-AAT was calculated from the sum of M-AAT and Z-AAT detected in serum.

Achieved >90% Editing of SERPINA1 Transcript Using GalNAc Delivery In Vivo

GalNAc

Day 0 7

3 mg/kg

14 49

Day 0 7

10 mg/kg

SERPINA1 RNA Editing

C57BL/6-PiZ Mouse

SERPINA1 RNA Editing % M-AAT Protein

Day

Oligo 1

Oligo 2

NSG-PiZ Mouse

92% editing

90% M-AAT

Note: Subcutaneous dosing Q2Dx3 at 3 or 10 mg/kg for each dose; editing efficiencies and protein percentages are measured on days 7, 14, and 49 by NGS and LC/MS, respectively. Proportion of M-AAT was calculated from the sum of M-AAT and Z-AAT detected in serum.

>70% editing at low doses (3x3 mg/kg) in vivo

Achieved >90% editing of SERPINA1 RNA translating into ~90% M-AAT levels using GalNAc delivery in vivo

Next catalyst: DC announcement expected in 2Q26

Transient & titratable subcutaneous GalNAc-conjugated oligonucleotide designed to address both lung and liver disease

Our RNA Editing Oligonucleotide Targeting AATD Has Potential to Be Best-in-Class

Disclaimer

Korro Bio Inc. published this content on May 15, 2026, and is solely responsible for the information contained herein. Distributed via Public Technologies (PUBT), unedited and unaltered, on May 15, 2026 at 20:46 UTC.