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1 Pioneering the Possible in Gene EditingMay 2025 Stephanie and Tristan
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2 Forward Looking StatementsThis presentation contains forward-looking statements and information within the meaning of The Private Securities Litigation Reform Act of 1995. The words‘‘anticipate,’’ ‘‘believe,’’ ‘‘continue,’’ ‘‘could,’’ ‘‘estimate,’’ ‘‘expect,’’ ‘‘intend,’’ ‘‘may,’’ ‘‘plan,’’ ‘‘potential,’’ ‘‘predict,’’ ‘‘project,’’ ‘‘target,’’ ‘‘should,’’ ‘‘would,’’ and similarexpressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Forward-lookingstatements in this presentation include statements regarding the initiation, timing, progress and results of the Company’s preclinical studies and its research anddevelopment programs, includingthe Company’s expectation to declare two development candidates for itsin vivoprograms by mid-2025 and achieve at leastin vivoone human proof of concept by year-end 2026, establish an additionalin vivotarget cell type/tissue beyond HSCs and the liver by the end of 2025 and achievein vivoproof of concept by 2027;the timing for the Company’s receipt and presentation of data from its preclinical studies; the potential of, and expectations for, theCompany’s product candidates; the timing or likelihood of regulatory filings and approvals, includingthe timing of the Company’s submission of any IND or CTA andability to commence clinical trials for itsin vivoprograms;and the Company’s expectations regarding cash runway into the second quarter of 2027. The Company maynot actually achieve the plans, intentions, or expectations disclosed in these forward-looking statements, and you should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a resultof various important factors, including:uncertainties inherent in the initiation and completion of preclinical studies; availability and timing of results from preclinicalstudies; expectations for regulatory approvals to conduct trials; and the availability of funding sufficient for the Company’s foreseeable and unforeseeable operatingexpenses and capital expenditure requirements. These and other risks are described in greater detail under the caption “Risk Factors” included in the Company’smost recent Annual Report on Form 10-K, which is on file with the Securities and Exchange Commission, as updated by the Company’s subsequent filings with theSecurities and Exchange Commission, and in other filings that the Company may make with the Securities and Exchange Commission in the future. Any forward-looking statements contained in this presentation speak only as of the date hereof, and the Company expressly disclaims any obligation to update any forward-lookingstatements, whether because of new information, future events or otherwise.
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3 In vivo gene editing – a simple IV infusion to cure a disease –will transform human therapeutics globally to the same degreethat mobile smart phones have transformed the communications business around the world.
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4 There is a Solution to the Recent Challenges of Gene Therapy and Gene Editing ProblemSolution• Recent slow launches• Low total addressable markets (TAMs)• Reimbursement challenges• High cost of goods• Low margins• Highly complex patient journeys• Curative business model• Many recent gene therapy launches pursued competitive indications with already high standards of care• Differentiated therapeutic approach to diseases • Diseases with higher TAMs• Simple, scalable, lower cost of goods• High margin in vivo delivery methods • Ability to treat more patients with less burdensome treatment regimen• Sustainable revenue growth for curative medicines through rapid development of therapies
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5 Has the solution A different approach focused on functional upregulation treatment strategy (proven by reni-cel).Solved for delivery using proprietary, targeted LNPs (tLNPs) that allow targeting of multiple tissues, including HSCs, liver, and other tissues using “plug ‘n play” process.Defined path to rapid development of new medicines with “plug ‘n play” in vivo editing using reprogrammable guide RNA by changing 20 nucleotides to create a new product for a new disease target.A leading gene editing platform supported by foundational IP estate.Driven management team with a proven track record of drug development and commercialization, strong domain expertise, and focus on execution.Strong cash position with operational runway into Q2 2027.
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6 Editas’ Differentiated In Vivo Gene Editing Upregulation Strategy Designed to Deliver First-to-Market and Best-in-Class Curative Medicines for Genetic DiseasesDiseases that can be addressed by protein reduction similar to ASO and siRNATherapeutic strategyGene Editing approachNon gene Editing modalityPatient populationAll patients (mutation agnostic) Functional upregulation*Knockdown Gene correctionsiRNA, antisense oligos, monoclonal antibody, and small molecule (pill)Subset of patients (single mutation)Other ApproachesTherapeutic potentialAll patients (mutation agnostic) First/best-in class opportunities for loss of function diseases; cannot be addressed via knockdownCorrection limited to subset of all patients with given disease*editing of regulatory region, e.g., 5’ or 3’ region to upregulate a wild type allele or functional homolog to address loss of function or deleterious mutations or or
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7 Reni-cel Provides Proof of Concept for Functional Upregulation Strategy and Validates Editing the HBG 1/2 Promoter •The safety profile was consistent with myeloablative busulfan conditioning and autologous HSCT •Reni-cel treatment showed promising results, with robust and clinically meaningful improvements, for gene editing at the HBG1/2promoters with AsCas12a•Patients achieved early correction of anemia, durable normalization of total Hb, and sustained increase in HbF ≥40% with pancellular distribution•Markers of hemolysis improved or normalized by Month 6•27 of 28 treated patients were VOE-free post-reni-cel infusion as of the data cutoff date •Early and sustained meaningful improvements were observed in pain, physical, and social patient-reported outcome domainsHb, hemoglobin; HbF, fetal hemoglobin; HBG1/2, γ-globin genes 1 and 2; HSCT, hematopoietic stem cell treatment; VOE, vaso-occlusive eventData cutoff date of Oct 29, 2024.Presented at the American Society of Hematology (ASH) Annual Meeting and Exposition, December 9, 2024.
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Demonstratedin vivo capabilities with devised novel HSC targeting strategy and proprietary LNPto deliver editing cargo Produced competitivepreclinical data set that outperforms data currently in the public domain Preclinical POC Data in In VivoHSC Editing Leverages Editas’ Gene Editing Expertise and Provides Foundation for LNP PlatformLeveragingreni-cel experience with validated target and enzymethat provides for development of a differentiated medicine for sickle cell disease and beta thalassemiaPotential for Best-in Class, First-in-ClassIn Vivo Medicine for Sickle Cell Disease and Beta Thalassemia • Foundation for an LNP Platform for Delivery to Extrahepatic Tissues • Ability to deliver gene editing cargo with HSC targeting moiety conjugated to our propriety LNP Platform• May provide delivery cargo to other tissues and cell types of interestProprietary LNP PlatformIn vivo gene editing medicine for sickle cell disease and beta thalassemia can expand the total addressable market (TAM)8
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CONFIDENTIAL – DO NOT DISTRIBUTE Therapeutically Relevant Level of Editing Achieved with Single Dose of Proprietary Targeted LNP in Mouse that Translates to NHP HSCs 9HBG1 / HBG2 PromoterHBG1 / HBG2PromoterTarget SiteHSCHSCHSPCCell Type47%48%36%Maximum % Editing Achieved >25% HBG1/2editing is predicted to be therapeutically relevant
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HBG1/2editing in HSCHBG1/2editing in HSPC HSPC editing ~1 week* or 2 weeks** after dosing~0.25%*~17%*~29%*~36%**~21%**LNP composition and process development optimization Switch targeting moietyLNP composition and process development optimization LNP composition optimization HSC editing 16 weeks after dosing48% %HBG1/2 indelPredicted therapeutic editing level10 Optimization of tLNP Platform Provides Capability to Achieve Efficient and SustainableHBG1/2 Editing in Humanized Mouse Model In vivo model: NBSGW mouse strain (NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ [NSG] crossed with C57BL/6J-KitW-41J/J [C57BL/6.KitW41]) engrafted, without irradiation, with human CD34+cells from peripheral blood after plerixafor mobilization of cells from bone marrow. HBG, γ-globin gene; HSC, hemopoietic stem cell defined as Lin-CD34+CD38-CD90+CD45RA-cells; HSPC, hemopoietic stem and progenitor cell defined as Lin-CD34+CD38-cells; LNP, lipid nanoparticle; tLNP, targeted LNP.
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% GFP+cellsUp to ~47% HBG1/2 editing observed in HSCs at 3 months after a single dose of LNP2 (moiety 2)~75% GFP+HSCs observed 24 hours after a single dose of LNP2Single IV dose of 2 mg/kg; no HSC mobilization %HBG1/2 indelPredicted therapeutic editing level of ≥25%*17% 38%Average % editing29% 47%Data from HSC of three individuals High Efficiency HSC Delivery Achieved Therapeutically Relevant HBG1/2Editing Levels After a Single Dose of Editas’ tLNP in Non-Human Primates Ongoing evaluation of further optimized formulations expected to achieve higher editing levels 11HSCs defined as CD34+CD90+CD45RA-cells based on Radtke S et al. 2017.1Clonal profile is consistent across all timepoints. *Therapeutically relevant editing threshold of ≥25% determined on the basis of editing dynamics and allogeneic HSC transplantation data from Fitzhugh CD et al. 2017.2GFP, green fluorescent protein; HBG, γ-globin gene; HSC, hematopoietic stem cell; IV, intravenous; LNP, lipid nanoparticle; tLNP, targeted LNP. 1. Radtke S et al. Sci Transl Med 2017; 9 (414): eaan1145. 2. Fitzhugh CD et al. Blood2017; 130 (17):1946–1948.
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Editas’ tLNPISH for cargoIHC for proteinLiver: High delivery in hepatocytes Liver: Minimal in hepatocytes Editas’ tLNP Shows Significant De-targeting of the Liver in Non-Human Primates 12Editas’ tLNP formulation containing surrogate GFP mRNA cargo was dosed to NHPs as a single IV infusion. Animals were taken down at 24 hours after dose and various non-target tissues were collected. GFP mRNA was detected in FFPE fixed tissue sections via ISH while the corresponding GFP protein was detected via IHC.FFPE, formalin-fixed, paraffin-embedded; GFP, green fluorescent protein; HBG, γ-globin gene; HSC, hematopoietic stem cell; ISH, in situ hybridization; IHC, immunohistochemistry; IV, intravenous; LNP, lipid nanoparticle; NHP, non-human primate; tLNP, targeted LNP. Standard LNP (comparator)
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13 Preclinical NHP PoC Validates High Efficiency Genomic Editing in Liver with First Delivery of AsCas12a Nuclease by Lipid Nanoparticle Editing data generated from whole tissue homogenateAsCas12a nuclease and target-specific gRNA delivered using Genevant proprietary LNP Maximum editing in liver with negligible editing in non-target tissues (PoC Tool) Robust serum biomarker reduction from the baseline (~80%)
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14 Disease Biomarker Reduction In Vivo Preclinical Proof of Upregulation Strategy Confirmed by Clinically Relevant Target Protein Increase Resulting in Significant Disease Biomarker Reduction in Undisclosed Target 1 Region 1 and Region 2 are blinded.AsCas12a EditingAsCas12a EditingRegion 1 Region 2012345 Region 1 Region 2-80-60-40-200Change from Baseline (%)In vivo achievement of clinically meaningful level (≥ 2-fold upregulation) of Target 1 protein expression in mice Target Protein Upregulation or
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Biomarker(% of Pre-Dose Level) Liver Functional Editng (%) RNA-LNP treatment of disease model mice OptimizedIn Vivo Preclinical Proof of Upregulation Strategy Induces Robust Reduction of Disease Biomarker in Undisclosed Target 1 15*Surrogate strategy for the orthologous region in the mouse genomeFunctional editing of regulatory region in the liver induces >80% biomarker reduction in a murine disease model Target Editing Biomarker Reduction
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16 In vivo PoC for Plug ‘n Play Delivery to Extrahepatic Cell Types Achieved with Editas’ Proprietary LNP Targeting Platform GFP: Green Florescent ProteinIHC: Immunohistochemistry Cell type 1Cell type 2Cell type 3 LNP tLNP LNP tLNP LNP tLNPTargeting Moiety 1Targeting Moiety 2Targeting Moiety 3 In vivo targeting to three extrahepatic cell types at ≥80% efficiency with our plug ’n play platform Specific Delivery of GFP to Target Cells in Humanized Mice
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17 A Capital Efficient In VivoGene Editing Company Demonstrates strength of Editas’ Foundational IP EstateUnlocks potential for future business development and licensing opportunities Provides upfront cash of $57M via non-dilutive financing Continued Execution of our Focus to Leverage our Foundational IP Estate for Access to Non-Dilutive Capital Editas Medicine Announces $50+ Million Monetization Financing with DRI Healthcare TrustO c t o b e r 0 3 , 2 0 2 4Strengthens balance sheet with non-dilutive capital to enable further pipeline development and related strategic priorities
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18 Editas’ Partnerships Validate Science and Value of IP EstateMultiple clinical-stage programs in development wilIrequire an IP License for use of CRISPR Cas9 or Cas12a technologyEditas is well positioned to capture value of IP and leverage non-dilutive financing to focus resources on in vivo pipeline developmentFuture IP Licensing Opportunities Editas’ Partners are Poised to Achieve Clinical Milestones in next 12-18 Months Current Collaborators and Partners (14 total programs)
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19 Declare Two in vivo Development Candidates by Mid-2025Present in vivo preclinical editing dataEstablish One Additional Target TissueDerive Revenue from Foundational IP•Candidate in hematopoietic stem cells (HSCs) for the treatment of beta thalassemia and sickle cell disease•Candidate in liver cells for an undisclosed indication•In vivo preclinical proof-of-concept in both HSCs and liver cells in large animal models•Disclose target cell type or tissue by end of 2025, beyond HSCs and liver cells•Building on the DRI Healthcare monetization, continue to issue sublicenses 2025 Key Anticipated Milestones
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20 2025-2027 Strategic Priorities Launch Clinical Trials for Multiple in vivo Programs in Multiple TissuesExpand the Range of Diseases Addressable by in vivo Gene Upregulation•Submit at least one IND/CTA by mid-2026•Begin at least one human clinical trial by 2H 2026•Potential for at least one late-stage clinical trial in 2H 2027•Achieve human proof-of-concept for at least one indication by year-end 2026•In vivo proof of concept in at least one tissue beyond HSCs and liver by 2027, demonstrating plug ‘n play potential of Editas’ proprietary extrahepatic LNP platformAchieve in vivo Human Proof of Concept by year-end 2026
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21 A different approach focused on functional upregulation treatment strategy (proven by reni-cel).Solved for delivery using proprietary, targeted LNPs (tLNPs) that allow targeting of multiple tissues, including HSCs, liver, and other tissues using “plug ‘n play” process.Defined path to rapid development of new medicines with “plug ‘n play” in vivo editing using reprogrammable guide RNA by changing 20 nucleotides to create a new product for a new disease target.A leading gene editing platform supported by foundational IP estate.Driven management team with a proven track record of drug development and commercialization, strong domain expertise, and focus on execution.Strong cash position with operational runway into Q2 2027.
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Additional Information
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23 DEVELOPMENT & COMMERCIAL PARTNERLATE-STAGE CLINICALEARLY-STAGE CLINICALIND ENABLINGPRECLINICALPROGRAM (OR DISEASE CANDIDATE)In Vivo HSC Editing – sickle cell diseaseIn vivo HSC Editing – beta thalassemiaLiver Upregulation Target 1Other Tissue Upregulation Target αβ T Cells (14 total programs)T Cells Programs Positioned for Development HEMOGLOBIN-OPATHIESOTHER ORGANS & TISSUESONCOLOGY