Korro Bio, Inc. · NASDAQ:KRRO
Korro Bio — Investor Day (January 2026)
54 slides from Korro Bio's investor day presentation, Jan 27, 2026
Slide 1: KRRO-121: A Potential First-in-Class Treatment for Ammonia Control
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: Today's Speakers
Today’s Speakers Ram Aiyar Loïc Vincent Todd Chappell Michelle Dinon Bruce Scharschmidt CEO CSO COO UCD Parent Clinician 3
Slide 4: Agenda
Agenda Expanding to New Biological Frontiers with RNA Editing Ram Aiyar, CEO Living with UCD: A Mother’s Perspective Michelle Dinon, UCD Parent Ammonia-driven Diseases: Urea Cycle Disorders Dr. Bruce Scharschmidt, Clinician and Hepatic Encephalopathy KRRO-121 Scientific Overview Loïc Vincent, CSO an
Slide 5: Expanding to New Biological Frontiers with RNA Editing
Expanding to New Biological Frontiers with RNA Editing Ram Aiyar, PhD, MBA Chief Executive Officer 5
Slide 6: 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 7: Living with UCD: A Mother's Perspective
Living with UCD: A Mother’s Perspective Michelle Dinon UCD Mother 7
Slide 8: Ammonia-driven Diseases: Urea Cycle Disorders and Hepatic Encephalopathy
Ammonia-driven Diseases: Urea Cycle Disorders and Hepatic Encephalopathy Bruce Scharschmidt, MD Hepatologist, Former CMO of Hyperion Therapeutics 8
Slide 9: Professional Background / Bruce F. Scharschmidt, MD
Professional Background / Bruce F. Scharschmidt, MD UCSF Faculty from 1977-1996: Professor of Medicine & Chief of GI • Helped start the UCSF liver transplant program with colleagues in surgery & medicine • Editor-in-Chief of the J. Clinical Investigation & President of the Am Society for Clin Invest
Slide 10: Ammonia (NH3): Most People's First Thoughts
Ammonia (NH3): Most People’s First Thoughts Ammonia is in household cleaners Surprised to learn that ammonia is in our bloodstream Imagine: You / your child are / is diagnosed with a urea cycle disorder 10
Slide 11: Urea Cycle Disorders (UCDs) are Cruel & Unforgiving
Urea Cycle Disorders (UCDs) are Cruel & Unforgiving You/your child becomes severely and acutely ill Your physician/pediatrician orders blood NH3, refers to a metabolic geneticist Metabolic geneticist confirms UCD Dx; advises: • Severely protein-restricted diet; perhaps with supplements • A short act
Slide 12: Ammonia Production & Disorders of Hyperammonemia
Ammonia Production & Disorders of Hyperammonemia Our Liver is Strategically Positioned The Urea Cycle Resides in the Liver Normal UCD ‘Alternate Pathway’ Drugs Triage & Cleansing • Sodium phenylbutyrate • Blood from the intestines (NaPBA, Buphenyl®) passes first through the liver • Glycerol phenylbu
Slide 13: UCDs: Overview
UCDs: Overview • Urea Cycle: enzymatic steps NH3 → urea • All autosomal recessive except X-linked OTCD • Genetically heterogeneous • HACs particularly a problem with proximal UCDs • The more severe the defect, the earlier the onset • Severity assessed clinically; measuring urea cycle activity involv
Slide 14: Ammonia Control: Lessons from the GPB Trials
Ammonia Control: Lessons from the GPB Trials Berry et al (J Ped 2001): “The goal of treatment is to maintain normal levels of plasma ammonia through the use of the low-protein diet and medication while allowing for normal growth.” But • No consensus among investigators regarding ammonia control • 24
Slide 15: UCD Patients Benefit from Tight Ammonia Control
UCD Patients Benefit from Tight Ammonia Control Genetics in Medicine; 2014 Time-to-event (HAC) ‘survival type’ analysis Methods: • Post-hoc analysis: > 1000 samples, 114 UCD pts < 0.5x ULN • Examined NH3 exposure (24-hour AUC) vs. HAC 0.5 – 1x ULN Results > 1x ULN • HAC risk, frequency correlates wi
Slide 16: Urea Cycle Disorders (UCDs): Unmet Need
Urea Cycle Disorders (UCDs): Unmet Need • UCD patients benefit from ‘tight’ ammonia control, but… • Treatment is tough • Particularly for school age children & adolescents • Severely restricted diets sometimes don’t resemble food • Sodium phenylbutyrate is unpleasant and causes body odor • Glycerol
Slide 17: What We Learned About HACs
What We Learned About HACs CLINICAL TRIAL DATA: HAC Triggers Among 49 Pediatric Patients on NaPBA Additional Considerations in the Year Prior to Enrollment* • Role of infection/intercurrent illness consistent with Trigger % data from UCDC sponsored Longitudinal Study (33%) * Intercurrent illness 26.
Slide 18: Some "Asymptomatic" Female OTCD Patients are Not Well
Some “Asymptomatic” Female OTCD Patients are Not Well • Most common subtype, X-linked • It was believed most females were asymptomatic • Dr. Andrea Gropman’s work has shown that ‘asymptomatic’ female patients exhibit subtle cognitive (executive, fine motor) and functional brain imaging abnormalities
Slide 19: Decompensated Cirrhosis and Hepatic Encephalopathy (HE)
Decompensated Cirrhosis and Hepatic Encephalopathy (HE) • Scarred liver impedes portal blood flow → portal Cirrhosis with PS Shunting hypertension & portal-systemic shunting (PSS) (i.e., shunting of blood around the liver) • 3 major manifestations of liver failure/PSS : HE, variceal bleeding, fluid
Slide 20: Ammonia Lowering is Effective in Secondary Prophylaxis of HE
Ammonia Lowering is Effective in Secondary Prophylaxis of HE 2012 AASLD Plenary / Hepatology; 2014 Time-to-event (HE event) ‘survival type’ analysis Methods: • RDBPC multi-national trial of GPB Hazard ratio: 0.56 GPB 95% CI: (0.32, 0.99) • 178 patients with ≥2 prior HE episodes in ≤ 6 mos P = 0.047
Slide 21: GPB Works by Ammonia Lowering
GPB Works by Ammonia Lowering Clinical Gastroenterology & Hepatology; 2016 HE Risk & Frequency vs. Fasting Ammonia Methods: • Post-hoc analysis: > 1000 ammonia samples from 178 pts • Examined fasting ammonia vs. risk, frequency of HE events • Binary logistic regression & Cox proportional hazard Resu
Slide 22: HE is Still a Big and Expensive Problem
HE is Still a Big and Expensive Problem HE Observational Study • 265 pts; 30 sites; ≥1 HE event ≤30 days; 72d mean F/U From Landis, 2016 • 72 (27%) pts experienced a total of 122 HE events • 23 (9%) / 13 (5%) had ≥ 2 / ≥ 3 HE events • 82% of patients with HE were on rifaximin • 85% of events resulte
Slide 23: HE Final Thoughts
HE Final Thoughts Why is HE still such a big problem? “Hepatic encephalopathy (HE) is … one of the • Drug compliance almost certainly an issue most debilitating manifestations of liver disease, severely affecting the lives of patients • Other complications better treated and their caregivers….. resu
Slide 24: Thank You
THANK YOU 24
Slide 25: KRRO-121 Scientific Overview and Preclinical Data
KRRO-121 Scientific Overview and Preclinical Data Loïc Vincent, PhD Chief Scientific Officer 25
Slide 26: 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 27: 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 28: 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 29: 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 30: 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 30
Slide 31: 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 32: 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 33: 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 34: 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 35: 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 36: 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 37: 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 37
Slide 38: 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 39: 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 40: 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 40
Slide 41: KRRO-121 Market Opportunity
KRRO-121 Market Opportunity Todd Chappell, MBA Chief Operating Officer 41
Slide 42: 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 43: 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 44: 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 45: KRRO-121 Product Profile for UCD Patients with Substantial Unmet Need
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 46: 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 47: 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 48: 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 49: 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 50: 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 51: Closing remarks
Closing remarks Ram Aiyar, PhD, MBA Chief Executive Officer 51
Slide 52: 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 52
Slide 53: Q&A
Q&A Ram Aiyar Loïc Vincent Todd Chappell Bruce Scharschmidt CEO CSO COO Clinician 53
Slide 54: Edit the message. Rewrite the future.
Edit the message. Rewrite the future. 54