Slides
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1 1 March 4th , 2025 TD Cowen Healthcare Conference Ram Aiyar, Ph.D., MBA Chief Executive Officer & President
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2 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, express or implied statements regarding expectations, hopes, beliefs, intentions or strategies of Korro Bio, Inc. (Korro) regarding the future including, without limitation, express or implied statements regarding: the benefits of Korro’s OPERA platform and its potential to develop transformative genetic medicines; the timing of and ability to advance three drug candidates to the clinic through 2027, advance a program towards the clinic in 2026 with liver delivery and activation of a biological pathway, and advance a third program targeting tissues outside of the liver; KRRO-110’s potential as a best-in-class therapy for patients with AATD; KRRO-110’s potential impact for patients including, its activity against neutrophil elastase and other proteases, potential favorability from a regulatory perspective, its ability to restore normal AAT levels for patients, its ability to achieve editing sufficient to impact patients’ lung and liver function, its ability to achieve meaningful levels of AAT, and its potential for a favorable dose-regimen; Korro’s ability to create value through multiple milestones in 2025; the timing of the interim data readout and completion of the Phase 1/2a clinical study for KRRO-110; the timing and nomination of a second development candidate in the liver with GalNac delivery; expanding Korro’s wholly owned pipeline; the ability to develop up to two therapeutic candidates for cardiometabolic diseases under the collaboration with Novo Nordisk; KRRO-110’s ability to restore therapeutic AAT levels in PiZZ patients and achieve 50% median editing to provide benefit in both lung and liver disease in PiZZ individuals; KRRO-110’s potential favorable therapeutic index, including in comparison to siRNA and mRNA; predictions of KRRO-110’s percent editing in humans based on the results and simulations of preclinical studies; KRRO-110’s potential to achieve monthly dosing within MZ range with a good therapeutic index; the clinical advancement of KRRO-110, including Korro's plans to expand its Phase 1/2a clinical study to other geographies; Korro’s cash runway, including its ability to complete a Phase 1/2a clinical study of KRRO-110 for AATD and advance other pipeline programs; among others. In addition, any statements that refer to projections, forecasts, or other characterizations of future events or circumstances, including any underlying assumptions, are forward-looking statements. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “might,” “plan,” “possible,” “potential,” “predict,” “project,” “should,” “strive,” “would,” “aim,” “target,” “commit,” and similar expressions may identify forward-looking statements, but the absence of these words does not mean that statement is not forward looking. Forward-looking statements are based on current expectations and assumptions that, while considered reasonable are inherently uncertain. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. Factors that may cause actual results to differ materially from current expectations include, but are not limited to, various factors beyond management’s control includingrisks inherent in biopharmaceutical development; risks associated with pre-clinical studies and clinical studies; and other risks associated with obtaining regulatory approvals and protecting intellectual property; as well as risks associated with general economic conditions; the possibilitythat Korro may be adversely affected by other economic, business, and/or competitive factors; other risks and uncertainties indicated from time to time in Korro’s filings with the SEC, including Item 1A. “Risk Factors” in Korro’s most recent Quarterly Report on Form 10-K or Form 10-Q filed with the SEC, as such may be amended or supplemented by its other filings with the SEC. Nothing in this presentation should be regarded as a representation by any person that the forward-looking statements set forth herein will be achieved or that any of the contemplated results of such forward-looking statements will be achieved. You should not place undue reliance on forward-looking statements in this presentation, which speak only as of the date they are made and are qualified in their entirety by reference to the cautionary statements herein. Except as required by law, Korro does not undertake or accept any duty to release publicly any updates or revisions to any forward-looking statements to reflect any change in their expectations or in the events, conditions or circumstances on which any such statement is based. This presentation does not purport to summarize all of the conditions, risks and other attributes of an investment in Korro. Industry and Market Data Certain information contained in this presentation relates to or is based on studies, publications, surveys and Korro’s own internal estimates and research. In this presentation, Korro relies on, and refers to, publicly available information and statistics regarding market participants in the sector in which Korro competes and other industry data. Any comparison of Korro to any other entity assumes the reliability of the information available to Korro. Korro obtained this information and statistics from third-party sources, including reports by market research firms and company filings. In addition, all of the market data included in this presentation involve a number of assumptions and limitations, and there can be no guarantee as to the accuracy or reliability of such assumptions. Finally, while Korro believes its internal research is reliable, such research has not been verified by any independent source and Korro has not independently verified the information. Trademarks This presentation may contain trademarks, service marks, trade names and copyrights of Korro or other third parties, which are the property of their respective owners. Solely for convenience, some of the trademarks, service marks, trade names and copyrights referred to in this presentation may be listed without the TM, SM © or ® symbols, but Korro will assert, to the fullest extent under applicable law, the rights of the applicable owners, if any, to its trademarks, service marks, trade names and copyrights.
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3 3 Developing Transformative Genetic Medicines for Rare and Highly Prevalent Diseases Editing RNA Without modifying DNA Activating Biological Pathways Learning from genetics Modular Platform Delivering drug to multiple cell types
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4 4 Poised For Value Creation Through 2027 With 3-2-1 Strategy *AATD represents a $3B market opportunity 3 Programs in the clinic Tissues targeted Editing Platform 2 1 • KRRO-110 for Alpha-1 Antitrypsin Deficiency (AATD)* as first program with liver delivery • 2nd program approaching the clinic in ‘26 with liver delivery and activation of biological pathway • 3rd program with a focus on targeting tissues outside the liver • Platform continuing to iterate on potency and delivery
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5 5 High Specificity Favorable Safety Margins KRRO-110: Potential best-in-class therapy for Patients with AATD Making alpha-1 antitrypsin (AAT) protein No bystander edit or abnormal variant of AAT Active against neutrophil elastase Potential favorable regulatory perspective High Efficiency Preclinical data with >50% editing in mice* Preclinical data demonstrating ~60uM AAT* Getting patients closer to "normal" AAT levels Higher the editing greater the impact on lung and liver function NOAEL at 5 mg/kg in Non-Human Primates with Single Dose in toxicology studies Supporting Data Potential Impact First participant dosed in January 2025; 2 SAD cohorts completed dosing *Data generated in NSG-PiZZ human transgenic model at 2 mg/kg RNA-Editing-Oligonucleotide Encapsulated in a Lipid Nanoparticle (LNP) Ability to achieve meaningful levels of AAT Potential for favorable dose-regimen
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6 Target RNA Adenosine Inosine ADARADAR 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’ Resultant therapeutic protein DNA with disease- causing mutation Non-viral intracellular delivery of Korro oligo designed to edit a specific adenosine on the target RNA 1 2 3 4 5 Harnessing an endogenous enzyme, ADAR, expressed in all human cells for a highly specific edit RNA Editing: Transiently Affecting anA-to-I Edit on RNA Using anOligonucleotide
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7 DNA Pre-mRNA mRNA Protein Edit a single A-to-I Modifying gene expression Current Focus Edit a single A-to-I • Repair a G->A mutation to correct the protein • Generate a de novo protein with preferred properties (can alter 12 amino acid sequences) TRANSCRIPTION PROCESSING TRANSLATION RNA Editing Enables Potential for High Impact in Broad Range of Disease Areas Human genetics guiding the possibilities
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8 Expertise in ADAR biology driving potency and translation Leveraging known Delivery driving derisked access to indications Expertise in Chemistry driving potency and drug designs Expertise in Machine Learning driving efficiency and Target ID OPERA: Our Approach for RNA Editing to GenerateProduct Candidates
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9 CONCEPT PROGRAM / INDICATION DELIVERY DISCOVERY PRECLINICAL DEVELOPMENT PHASE 1 PHASE 2 PHASE 3 Repairing a pathogenic variant KRRO-110 AATD LNP (IV) De novo protein to inhibit degradation Rare metabolic disorder GalNAc (SC) De novo protein to overcome LoF and GoF 1 Amyotrophic lateral sclerosis Undisclosed De novo protein to modulate currents Subsets of pain Undisclosed Repairing a pathogenic variant Parkinson's disease Undisclosed Undisclosed Cardiometabolic Undisclosed AAT Phase 1/2a - Interim data in 2H '25 Undisclosed DC in '25 TDP43 Robust Pipeline with Multiple High-Value Targets Up to 2 Targets LRRK2 1De Novo protein variant to prevent toxic gain of function (GoF) with TDP43 aggregation, and still continue downstream signaling by overcoming toxic Loss-of-function (LOF) Nav1.7
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10 10 1 Cash, cash equivalents and marketable securities of $169.1 million as of September30, 2024 Korro is Poised for Value CreationThrough Multiple Milestones in 2025 Cash runway into 2H ’261 enables multiple milestones for KRRO-110 and other pipeline programs Initiated KRRO-110 study (REWRITE) Advanced multiple discovery targets Announced partnership with Novo Nordisk Closed a $70M PIPE Appointed key Board and team members 2024 Accomplishments Share Interim clinical data for KRRO-110 from REWRITE study in 2H’25 Nominate a candidate with SC delivery (GalNAc) in Liver in ’25 that can create a de novo protein variant Progress and expand a wholly owned pipeline Progress partnership with Novo Nordisk in cardiometabolic diseases with high prevalence 2025 Anticipated Milestones
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11 Oligonucleotide Promoted Editing of RNA (OPERA) Our Approach
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12 Gen 1.0: A single-stranded, anti-sense oligonucleotide RNA editor High target efficiency High target specificity Computational efficiency Leveraging chemistry Leveraging delivery CHORD Designed to have… Customized High-fidelity Oligonucleotides for RNA Deamination (CHORD)
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13 Control KB-9873 KB-7532 0 20 40 60 80 100 Editing (%) Day 1 Day 4 Learning from Structure Improving Editing efficiency* Potency increase with new analog Developing Novel Chemistry *3mg/kg oligo formulated in MC3 LNP injected IV Structural Biology Insights of ADAR binding Enable Potency Boosts In Vivo
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14 Note: GalNAc, LNP and CNS data from C57BL/6 mice Demonstrated Editing of RNA Across Multiple Tissue Types Liver with Lipid Nanoparticle Liver with Receptor Uptake CNS with "Naked" Delivery Day 7 Day 14 0 20 40 60 80 KB-2330 % Editing (ACTB) Day 1 Day 7 Day 14 0 20 40 60 80 KB-9775 % Editing (ACTB) Cervical Thoracic Lumbar 0 20 40 60 80 KB-8720 % Editing (ACTB) IT Dose (50 ug; Day 4)IV; MC3 LNP; 2 mpk SC; 10 mpkx5; GalNAc Delivery
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15 Delivering a Potential Best-in-Class Candidatewith KRRO-110 Alpha-1 Antitrypsin Deficiency (AATD)
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16 Note: AAT protein is encoded by the gene SERPINA1. The E342K mutation (G to A) in SERPINA1 (Z allele) is the most frequent mutation and causes severe lung and liver disease *Z-AAT not as active as M-AAT **Source: Alpha-1 Foundation. Numbers reflected here are carrier of ZZ genotypes Minimal inhibition of lung neutrophil elastase Reduced levels of Z-AAT secreted Mutated AAT polymerizes and aggregates in liver cells ZZ Genotype (fibrotic liver and decreased lung function) Normal levels of M-AAT secreted Inhibits neutrophil elastase in the lung M-AAT MM Genotype (normal liver and lung) Z-AAT* ~100K PiZZ adult patients in U.S.** AATD Most Commonly Caused by aSingle Missense (G-to-A) Mutation in SERPINA1 Gene in the Liver
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17 KRRO-110: CHORD Encapsulated inanLNP with Human* Exposure SERPINA1 mRNA Hepatocyte CHORD KRRO-110 PiZZ Liver M-AAT Z-AAT IV DELIVERY ADAR Note: Editing is a function of number of transcripts in each cell. Editing refers to data from preclinical models *LNP contained in KRRO-110 has been dosed in multiple clinical trials A Secreted Z-AAT Polymers In liver LNP Licensed from Genevant Depending on editing levels some Z-aggregates in liverEdited mRNA X 100 Edited + Mutant mRNA % editing =
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18 0 10 20 30 40 50 KRRO-110 Aims to Restore Therapeutic AAT Levels in PiZZ Patients 1Nakanishi T. et al. Eur Respir J. 2020 Dec 10;56(6):2001441 2 Chronic obstructive pulmonary disease 3In non-smokers Serum AAT levels (μM) = Median AAT for genotype Odds Ratio1 MM MZ ZZ COPD2 1.0 1.0 8.8 Cirrhosis 1.0 1.5 7.8 Korro’s Objectives • >50% editing provides total AAT levels within the MZ range with o No lifetime risk for lung disease3 o Low lifetime risk for liver disease • Korro’s goal for ~50% median editing has the potential to provide benefit in both lung and liver disease in PiZZ individuals
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19 Achieved 45µM of M-AAT levels at week 13 Achieved EditingGoal of >50% with Meaningful Secreted AAT levels Achieved a range of editing needed for potential benefit Week 9 Results Control Week 1 Week 9 Week 13 0 20 40 60 80 100 % Editing (E342K) KRRO-110; 2mg/kg Peak* (predicted) Trough (predicted) Week 1 Week 13 Control 2 mg/kg Control 2 mg/kg Control 2 mg/kg 0 20 40 60 0 500 1000 1500 2000 2500 3000 3500 AAT concentration (μM) AAT concentration (μg/mL) M-AAT Z-AAT 378070Week 9 *predicted based on modeling
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20 KRRO-110 Reduces Z-AAT Protein and Toxic Aggregates in Liver Vehicle KRRO-110 PAS-D Staining Z-AAT Staining *data shown from transgenic PiZ mice on C57BL/6 background Histopathology data demonstrates potential to positively impact liver manifestations in AATD
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21 SERPINA1 Surrogate Editors Demonstrate Good Translation to Higher Species Surrogate SERPINA1 design: KB-1494-GVT KRRO-110 site E342K KB-1494-GVT site (few bases away) SERPINA1 mRNA Observations for KB–1494-GVT in PiZ C57BL/6 and Cyno KB-1494-GVT edits at ~2x in Cynos relative to PiZ mouse 2mg/kg (single dose) 0 10 20 0 20 40 60 80 100 Time (day) Editing (%) simulation result prediction
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22 KRRO-110: Progressing a Potential Best-in-Class Compound inthe Clinic Preclinical data, toxicology studies and data modeling demonstrate the potential to achieve monthly dosing within MZ range with a good therapeutic index ✓ Achieved required editing efficiency ✓ Reduction in Z-AAT protein ✓ Secreted functional M-AAT Preclinical Efficacy ✓ No off-target effects ✓ Well tolerated at 5 mg/kg in NHPs ✓ No signal of ASO-class effects Preclinical Safety ✓ Editing in MZ hepatocytes ✓ Demonstrate scaling in higher species (NHPs) ✓ Predicting >70% editing in humans at Cmax (peak) Demonstrated translation
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23 A Phase 1/2a, Two Part, Single- and Multiple-Dose Escalation Study • Study initiated in Australia, expanding geographies • Total enrollment = Up to 64 adult participants with PiMM or PiZZ genotype • Primary endpoints: Safety and tolerability • Secondary endpoints: PK, Total-AAT, M-AAT, and functional anti-protease activity Clinicaltrials.gov | NCT06677307 Dosing initiated January 2025; Two cohorts enrolled; Interim data anticipated in 2H’25 2:1 (Drug : PBO) 2:1 (Drug : PBO) Part 1 = SAD Part 2 = MAD PiMM PiZZ Drug Only - Open Label
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24 Positioned for Growth and Value Creation in 2025 and Beyond Share Interim clinical data for KRRO-110 from REWRITE study in 2H’25 Progress partnership with Novo Nordisk incardiometabolic diseases with high prevalence Cash runway into 2H’261 enables multiple milestones for KRRO-110 and other pipeline programs 1 Cash, cash equivalents and marketable securities of $169.1 million as of September30, 2024 Nominate a 2nd candidate for Liver indication in’25 that can create a de novo protein variant Progress and expand a wholly owned pipeline
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25 25 Edit the message. Rewrite the future.