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1 Pioneering the Possible in Gene Editing January 2025 Stephanie and Tristan
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2 Forward Looking Statements This 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 similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Forward-looking statements in this presentation include statements regarding the initiation, timing, progress and results of the Company’s preclinical studies and its research and development programs, including the Company’s expectation to declare two development candidates for its in vivo programs by mid-2025, establish an additional in vivo target cell type/tissue beyond HSCs and the liver by the end of 2025 and achieve in vivo proof of concept by 2027; the timing for the Company’s receipt and presentation of data from its preclinical studies, including presenting further in vivo HSC and liver data in 2025; the potential of, and expectations for, the Company’s product candidates; the timing or likelihood of regulatory filings and approvals, including the timing of the Company’s submission of any IND or CTA and ability to commence clinical trials for its in vivo programs; and the Company’s expectations regarding cash runway into the second quarter of 2027. The Company may not 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 result of various important factors, including: uncertainties inherent in the initiation and completion of preclinical studies; availability and timing of results from preclinical studies; expectations for regulatory approvals to conduct trials; and the availability of funding sufficient for the Company’s foreseeable and unforeseeable operating expenses and capital expenditure requirements. These and other risks are described in greater detail under the caption “Risk Factors” included in the Company’s most 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 the Securities 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-looking statements, 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 degree that 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 Problem Solution • 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 Diseases Diseases that can be addressed by protein reduction similar to ASO and siRNA Therapeutic strategy Gene Editing approach Non gene Editing modality Patient population All patients (mutation agnostic) Functional upregulation* Knockdown Gene correction siRNA, antisense oligos, monoclonal antibody, and small molecule (pill) Subset of patients (single mutation) Other Approaches Therapeutic potential All patients (mutation agnostic) First/best-in class opportunities for loss of function diseases; cannot be addressed via knockdown Correction 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
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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 HBG1/2 promoters 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 domains Hb, hemoglobin; HbF, fetal hemoglobin; HBG1/2, γ-globin genes 1 and 2; HSCT, hematopoietic stem cell treatment; VOE, vaso-occlusive event Data 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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Demonstrated in vivo capabilities with devised novel HSC targeting strategy and proprietary LNP to deliver editing cargo Produced competitive preclinical data set that outperforms data currently in the public domain Preclinical POC Data in In Vivo HSC Editing Leverages Editas’ Gene Editing Expertise and Provides Foundation for LNP Platform 8 Leveraging reni-cel experience with validated target and enzyme that provides for development of a differentiated medicine for sickle cell disease and beta thalassemia Potential for Best-in Class, First-in-Class In 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 interest Proprietary LNP Platform In vivo gene editing medicine for sickle cell disease and beta thalassemia can expand the total addressable market (TAM)
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9 High Levels of In Vivo HBG1/2 Gene Editing Achieved in HSPCs with Optimization of a Proprietary LNP and Novel Targeting Strategy in Mice with Human HSPC HBG1/2 editing in HSPC Switch targeting moiety LNP formulation optimization ~29% ~10% ~0.25% Data from pool of HSPC from 3 mice 4 days post dosing Data from HSPC of 5 individual mice 6 days post dosing LNP2 (moiety2) 0 10 20 30 40% HBG1/2 indel LNP3 (moiety2) 0 10 20 30 40% HBG1/2 indel LNP1 (moiety1) 0 10 20 30 40% HBG1/2 indel untreated LNP3 0 10 20 30 40 50 % HbF+ cells (F-cells) HBG1/2 editing in HSCs Data from HSCs pooled from 7 mice after 4 weeks of treatment HbF induction in erythroid cells LNP optimization ~40% HSC 0 10 20 30 40 50%HBG1/2 indel Each data point from pool of HSPC from 3 mice, 7 days post dosing Preclinical PoC achieved for potential treatment of SCD and Beta thalassemia by a clinically validated strategy after a single dose of Editas’ proprietary tLNP 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. HSPC: Hematopoietic stem and progenitor cells; HSPC defined as Lin-CD34+CD38- cells; HSC defined as Lin-CD34+CD38-CD90+CD45RA- cells; % indel indicates level of allelic editing, % HbF+ (Fetal hemoglobin positive) cells by flow cytometry LNP3 (moiety 2)
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10 Ongoing evaluation of further optimized formulations, e.g., LNP3 (moiety 2) expected to achieve higher therapeutic editing levels ~17% HBG1/2 editing in HSCs observed 7 days after a single dose of LNP2 (moiety 2) ~75% GFP+ HSCs observed 24 hours after a single dose of LNP2 (moiety 2) High Efficiency HSC Delivery Approaching Therapeutic Editing Levels Achieved After a Single Dose of LNP2 in Non-human Primates GFP mRNA delivery and HBG1/2 editing of HSCs after single dose of LNP2 (moiety 2) Data from HSC of 3 individual NHPs 24 hours post dosing Data from HSC of 3 individual NHPs 7 days post dosing LNP2 (moiety2) 0 5 10 15 20 25 30% HBG1/2 indel Predicted therapeutic editing level Sham LNP2 (moiety2) 0 20 40 60 80 100% GFP+ cells HSC: Hematopoietic stem cells defined as CD34+CD90+CD45RA- cells based on Radtke, S. Kiem, HP, et al. (2017). Sci Transl Med 9(414):eaan1145 GFP: Green fluorescent protein
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11 Preclinical NHP PoC Validates High Efficiency Genomic Editing in Liver with First Use of AsCas12a Nuclease Delivery by Lipid Nanoparticle Editing data generated from whole tissue homogenate AsCas12a 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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12 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 Editing AsCas12a Editing Region 1 Region 2 0 1 2 3 4 5Fold Change Target Protein Region 1 Region 2 -80 -60 -40 -20 0 Change 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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13 In vivo PoC for Plug ‘n Play Delivery to Extrahepatic Cell Types Achieved with Editas’ Proprietary LNP Targeting Platform GFP: Green Florescent Protein IHC: Immunohistochemistry Cell type 1 Cell type 2 Cell type 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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14 A Capital Efficient In Vivo Gene Editing Company Demonstrates strength of Editas’ Foundational IP Estate Unlocks 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 Trust October 03, 2024 Strengthens balance sheet with non-dilutive capital to enable further pipeline development and related strategic priorities
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15 Editas’ Partnerships Validate Science and Value of IP Estate Multiple clinical-stage programs in development wilI require an IP License for use of CRISPR Cas9 and Cas12a Technology Editas is well positioned to capture value of IP and leverage non-dilutive financing to focus resources on in vivo pipeline development Future 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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16 Declare Two in vivo Development Candidates by Mid-2025 Present in vivo preclinical editing data Establish One Additional Target Tissue Derive 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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17 2025-2027 Strategic Priorities Launch Clinical Trials for Multiple in vivo Programs in Multiple Tissues Expand the Range of Diseases Addressable by in vivo Gene Upregulation • Submit at least one IND/CTAs 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 platform Achieve in vivo Human Proof of Concept by year-end 2026
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18 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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20 PROGRAM (OR DISEASE CANDIDATE) PRECLINICAL IND ENABLING EARLY-STAGE CLINICAL LATE -STAGE CLINICAL DEVELOPMENT & COMMERCIAL PARTNER In Vivo HSC Editing – sickle cell disease In vivo HSC Editing – beta thalassemia Liver Upregulation Target 1 Other Tissue Upregulation Target αβ T Cells (14 total programs) γδ T Cells iNK Cells Programs Positioned for Development HEMOGLOBIN -OPATHIES OTHER ORGANS & TISSUES ONCOLOGY