Korro Bio, Inc. · NASDAQ:KRRO
Korro Bio — Investor Day (January 2026)
32 slides from Korro Bio's investor day presentation, Jan 27, 2026
Slide 1: KRRO-121: A Potential First-in-Class Treatment for Ammonia Control
Exhibit 99.1 Analyst Day 2026 KRRO-121: A Potential First-in-Class Treatment for Ammonia Control January 27th, 2026 1
Slide 2: Forward-Looking Statements and Disclaimers
Forward-Looking Statements and Disclaimers Forward-Looking Statements Certain statements in this presentation may constitute “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements include, but are not limited to
Slide 3: Expanding to New Biological Frontiers with RNA Editing
Expanding to New Biological Frontiers with RNA Editing Ram Aiyar, PhD, MBA Chief Executive Officer 3
Slide 4: Developing Transformative Genetic Medicines for Rare and Highly Prevalent Diseases
Developing Transformative Genetic Medicines for Rare and Highly Prevalent Diseases Modulate Protein Function (Activate pathway) Editing RNA TRANSLATION Without permanently modifying DNA RNA Normal Protein Modular Delivery Potential to deliver to multiple cell types TRANSLATION Edited RNA Protein Var
Slide 5: KRRO-121 Scientific Overview and Preclinical Data
KRRO-121 Scientific Overview and Preclinical Data Loïc Vincent, PhD Chief Scientific Officer 5
Slide 6: Mechanism: Stabilizing Glutamine Synthetase to Clear Ammonia
Mechanism: Stabilizing Glutamine Synthetase to Clear Ammonia Glutamine Synthetase (GS) is a critical ammonia clearing mechanism Genetic evidence uncovers a key amino acid modification that can augment GS protein stability Ammonia-lowering benefits of stabilized GS activity may address substantia
Slide 7: Two Complementary Pathways for Ammonia Clearance: Urea Cycle and Glutamine Synthetase
Two Complementary Pathways for Ammonia Clearance: Urea Cycle and Glutamine Synthetase (GS) Urea Cycle Glutamine Synthetase Ammonia Glutamate Ammonia OTC CPS-1 ARG Urea Cycle ASS Urea Glutamine synthetase ASL Glutamine Expressed Expressed in many tissues, primarily in liver including liver, brain, an
Slide 8: Degradation of GS Controlled by Levels of Glutamine
Degradation of GS Controlled by Levels of Glutamine Degradation Mechanism: Acetylation Glutamine Drives Degradation of GS of Key N-terminal Residues Glutamate Ammonia Low High glutamine glutamine N Glutamine synthetase Lys Lys N Ac Ac Glutamine Glutamine Ubiquitination Degradation GS Degradation syn
Slide 9: Human Genetic Evidence Supports Stabilization of GS by Preventing Degradation
Human Genetic Evidence Supports Stabilization of GS by Preventing Degradation Loss of Function Gain of Function N Glutamine Glutamine synthetase synthetase No N-terminal Asn Lys degron Acetylation mimic prone to degradation GS stability Ammonia GS Stability Ammonia Stable activity Patient with Lys14
Slide 10: Hypothesis: Preventing GS Degradation Will Stabilize the Protein and Enable Increased Ammonia Clearance
Hypothesis: Preventing GS Degradation Will Stabilize the Protein and Enable Increased Ammonia Clearance Glutamate Ammonia Liver-specific GS Glutamine modification may synthetase prevent degradation, N increase ammonia Arg Lys clearance GS degradation prevented Glutamine 10
Slide 11: Our Approach: Liver-specific, GalNAc-ASO to Generate a Stable GS Variant
Our Approach: Liver-specific, GalNAc-ASO to Generate a Stable GS Variant Liver directed editing (GalNAc delivery) GalNAc Glutamine Designed to synthetase maintain De novo GS variant + A I (G) Arg Lys N consistent ammonia clearance KRRO-121 GS mRNA Edited GS mRNA De novo GS variant capacity KRRO-121:
Slide 12: KRRO-121 Stabilized GS in UCD-derived Human Cell Models
KRRO-121 Stabilized GS in UCD-derived Human Cell Models OTC iPSC KRRO-121 KRRO-121 Stabilized GS in OTC-Deficient iPSC-Derived Hepatocytes 3 non treated GS degradation Similar results 10 mM NH4Cl Fold Change to Vehicle in ASS1-deficient 2 ✱✱✱ iPSC-derived hepatocytes GS remained stable upon 1.0 1.0
Slide 13: Ammonia Reduction in OTC-Deficient Mice Challenged with Ammonia
Ammonia Reduction in OTC-Deficient Mice Challenged with OTCspf/ash Ammonia Supports Clinical Activity, Diet Liberalization Improved Clearance in Ammonia Challenge Nonsignificant Increase in Supports Potential to Increase Protein Intake Plasma Glutamine Levels 2500 1000 Vehicle Mouse-optimized oligo
Slide 14: De Novo GS Variant Enabled Ammonia Control in OTC Mice Under Protein Load
De Novo GS Variant Enabled Ammonia Control in OTC Mice OTCspf/ash Under Protein Load, with Stable Isotope Tracer Validating MOA Increased Plasma Decreased Plasma Increased Total Liver N-15 Glutamine Ammonia GS Concentration 4000 1000 1.5 Vehicle Mouse-optimized oligo AUC Glutamine Conc (µM) x Fold C
Slide 15: Ammonia Reduction in CPS-1 Deficient Mice Further Validates Pan-UCD Applicability
Ammonia Reduction in CPS-1 Deficient Mice Further Validates CPS-1 Potential Pan-UCD Applicability and Diet Liberalization Reduction in Ammonia Nonsignificant Increase in Following Ammonia Challenge Plasma Glutamine Levels Vehicle 2000 p < 0.05 1500 Mouse-optimized oligo ns ns 1500 Blood Gln (μM) Amm
Slide 16: KRRO-121 Significantly Reduced Ammonia Levels in Humanized Liver Mouse Model
KRRO-121 Significantly Reduced Ammonia Levels in Basal State and PXB Following Ammonia Challenge in Humanized Liver Mouse Model KRRO-121 Stabilized GS Variant and Reduction in Enhanced Ammonia Clearance Steady Glutamine Normal GS Protein Levels Basal Ammonia in Challenge Post-Challenge Predose ammon
Slide 17: KRRO-121 Showed No Increase in Astrocyte Activation in Brain
KRRO-121 Showed No Increase in Astrocyte Activation in Brain OTCspf/ash KRRO-121 1 mm 5 mm GFAP+ cells represented as brown dots 1 mm 5 mm Note: Vehicle or KRRO-121 dosed at 20 mg/kg-SC daily on Days 0-4. Editing and GFAP measured following ammonia challenge (150 mg/kg) on Day 14 17
Slide 18: KRRO-121 Displayed Strong Liver Uptake and No Adverse Findings in Non-Human Primates
KRRO-121 Displayed Strong Liver Uptake and No Adverse Findings in Non-Human Primates KRRO-121 >90% Delivery of Confirmed Liver Localization of No Changes in Liver or Kidney Function KRRO-121 to Liver KRRO-121 with Pericentral GS KRRO-121 (QWx3, Monkey) - 6h post 3rd dose Liver: 10 mg/kg 30 mg/kg 2.0
Slide 19: KRRO-121: A Potential First-in-class Treatment For Ammonia Control
KRRO-121: A Potential First-in-class Treatment For Ammonia Control Preclinical Activity Preclinical Safety Demonstrated Translation Pan-UCD potential impacting NHP: No adverse safety signals in Production of stable, de novo GS multiple UCD subtypes repeat QWx3 dose range finding tox variant wh
Slide 20: KRRO-121: Anticipated Regulatory Filing in Second Half of 2026
KRRO-121: Anticipated Regulatory Filing in Second Half of 2026 2025 2026 H2 H1 H2 DC Regulatory Filing Nominated Analyst Day for FIH Trial KRRO-121 Compelling product profile for controlling ammonia expected to drive strong patient engagement and recruitment 20
Slide 21: KRRO-121 Market Opportunity
KRRO-121 Market Opportunity Todd Chappell, MBA Chief Operating Officer 21
Slide 22: KRRO-121 Has Blockbuster Potential in Multiple Indications
KRRO-121 Has Blockbuster Potential in Multiple Indications Urea Cycle Hepatic Disorders Encephalopathy Addressable 4,200 U.S. 1 80,000 U.S. 2 Patients 5,100 EU + UK1 150,000 EU + UK3 Market Opportunity $1.5B $2B+ Note: 1. Severe late-onset UCD patients; 2. Patients prescribed rifaximin +/- lactulose
Slide 23: Plasma Ammonia Significantly Impacts Pathology Across Multiple Diseases
Plasma Ammonia Significantly Impacts Pathology Across Multiple Diseases Ammonia Pathology High ammonia leads to: ‒ Neurological impairment, potentially permanent Diet & metabolism Normal ‒ Frequent hospitalization Clearance Normal excretion through kidneys ‒ Highly restricted diet ‒ Elevated infec
Slide 24: Uncontrolled Ammonia is a Persistent Danger for UCD Patients
UCD Uncontrolled Ammonia is a Persistent Danger for UCD Patients Ammonia Frequently >1.5x ULN in UCD, Leading to Increased Hyperammonemia Risk 200 175 150 Ammonia control is highly challenging in UCD patients Ammonia (µmol/L) 125 100 today, often requiring nitrogen 75 scavengers + strict diet that 5
Slide 25: KRRO-121 Designed to Have a Compelling Product Profile for UCD Patients
UCD KRRO-121 is Designed to Have a Compelling Product Profile to Potentially Address UCD Patients with Substantial Unmet Need Differentiated Ammonia-Lowering Approach De novo hepatic GS variant with enhanced stability, designed to enable robust ammonia clearance capacity via chronic maintenance ther
Slide 26: KRRO-121 Can Potentially Address Patients Across All UCD subtypes
UCD KRRO-121 Can Potentially Address Patients Across All UCD subtypes U.S. UCD Epidemiology UCD Subtypes ARG1 + HHH + NAGS + Citrin 6,500 CPS1 UCD patients ASS ASL 4,600 post-neonatal onset1 OTC 4,200 5,100 additional addressable severe2 patients in EU + UK Note: 1. Onset of symptoms at age >1 month
Slide 27: Ammonia Measurements in Uncontrolled HE Patients Are Frequently Above Normal
HE Ammonia Measurements in Uncontrolled HE Patients Are Frequently Above Normal, Correlating with Higher HE Risk HE Events Correlate with Ammonia Ammonia Elevated in Many Severe / Recurring HE Patients1 Glycerol Phenylbutyrate Ammonia Measurements: HE Patient Phase 2 HALT-HE Study Severe / Recurring
Slide 28: Elevated Ammonia Levels Are Associated with a Greater Healthcare Burden in HE
HE Elevated Ammonia Levels Are Associated with a Greater Healthcare Burden in HE High Ammonia Significantly Increases Hospitalization Risk HE-related1 All-cause ** 4 4 >2-fold increase in HE-related *** hospitalization for addressable HE hospitalizations / patient 3 3 patients2 vs all severe / rec
Slide 29: KRRO-121 Also Has an Opportunity to Address Significant Unmet Need in HE
HE KRRO-121 Also Has an Opportunity to Potentially Address Significant Unmet need in HE Differentiated Ammonia-Lowering Approach De novo hepatic GS variant with enhanced stability, designed to enable robust ammonia clearance capacity via chronic maintenance therapy Direct Improved Convenient Reducti
Slide 30: Up to ~80K Addressable Patients in the U.S. with Severe / Recurring HE
HE Up to ~80K Addressable Patients in the U.S. with Severe / Recurring HE May Benefit from Ammonia-Lowering Treatment U.S. HE Epidemiology 2,200,000 Additional Patients with cirrhosis1 opportunity can be unlocked in 140,000 Severe / recurring HE2 prevention of initial HE episode Up to 80,000 150,000
Slide 31: Closing remarks
Closing remarks Ram Aiyar, PhD, MBA Chief Executive Officer 31
Slide 32: Key Takeaways from KRRO-121
Key Takeaways from KRRO-121 Significant unmet medical need for controlling ammonia Robust scientific / genetic evidence supporting GS stabilization approach Transformative potential to impact patients Vision for the future as a leader in modulating disease biology 32