Slides
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Meet Andrew and JJ, living with Duchenne muscular dystrophy Corporate Presentation January 2026
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Disclaimer This presentation has been prepared by Entrada Therapeutics, Inc. (“Entrada”) and shall not constitute an offer to sell or a solicitation of an offer to buy securities or an invitation or inducement to engage in investment activity nor shall there be any sale of securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification of such securities under the securities law of any such jurisdiction. Entrada has filed a shelf registration statement (including a prospectus) with the Securities and Exchange Commission (the “SEC”) for the offering to which this presentation relates. Before you invest in any securities of Entrada, you should read the prospectus in that registration statement and any other documents Entrada has filed with the SEC for more complete information about Entrada and the offering. You may get these documents for free by visiting EDGAR on the SEC website at www.sec.gov. This presentation contains express and implied forward-looking statements that involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this presentation, including statements regarding Entrada's strategy, future operations, prospects and plans, objectives of management, the validation and differentiation of Entrada’s approach and EEV platform and its ability to provide a potential treatment for patients, expectations regarding Entrada’s Phase 1/2 MAD clinical study of ENTR-601-44, including the timing of data from Cohort 1 in the second quarter of 2026, Cohort 2 by year-end of 2026 and Cohort 3 to follow, expectations regarding the data from the clinical study of ENTR-601-44, including expected results, translatability to derisk Entrada’s DMD clinical portfolio and ability to support U.S. Accelerated Approval, expectations regarding initiation of the planned ELEVATE-44-102 study in the U.S. in the first half of 2026, expectations regarding Entrada’s Phase 1/2 MAD clinical study of ENTR-601-45, including the timing of data from Cohort 1 in mid-2026, with data from Cohort 2 and Cohort 3 to follow, expectations regarding the timing of regulatory filings in the EU for the planned Phase 1/2 MAD clinical study of ENTR-601-50 in the second half of 2026 and initiation by the end of 2026 pending clearance, expectations regarding the timing of global regulatory filings for the planned clinical study of ENTR-601-51 in 2026 , the ability to recruit for and complete global Phase 2 clinical studies of ENTR-601-44, ENTR-601-45, ENTR-601-50 and ENTR-601-51 and to obtain U.S. Accelerated Approval for each program, the potential therapeutic benefits of Entrada’s EEV product candidates and the ability to advance therapeutic candidates in indications beyond neuromuscular disease, including but not limited to ocular disease, expectations regarding the timing of nomination of a second clinical candidate for ocular disease in 2026, the continued development and advancement of ENTR-601-44, -45, -50 and -51 for the potential treatment of DMD and ENTR-801 for the potential treatment of Usher syndrome type 2A and the partnered product candidate VX-670 for the potential treatment of DM1, expectations regarding the progress and success of Entrada’s collaboration with Vertex, including completion of enrollment and dosing of the MAD portion of the global Phase 1/2 study of the VX-670 program in mid-2026, the ability to continue to expand and develop additional therapeutic programs and modalities, including further exon skipping programs and the sufficiency of Entrada’s cash resources into the third quarter of 2027, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. The words “anticipate, ” “believe, ” “continue, ” “could, ” “estimate, ” “expect, ” “intend, ” “may, ” “might, ” “objective, ” “ongoing, ” “plan, ” “predict, ” “project, ” “potential, ” “should, ” or “would, ” or the negative of these terms, or other comparable terminology are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Entrada 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 identification and development of product candidates, including the conduct of research activities and the initiation and completion of preclinical studies and clinical studies; uncertainties as to the availability and timing of results from preclinical and clinical studies; the timing of and Entrada’s ability to submit and obtain regulatory clearance and initiate clinical studies; whether results from preclinical studies or clinical studies will be predictive of the results of later preclinical studies and clinical studies; whether Entrada's cash resources will be sufficient to fund Entrada's foreseeable and unforeseeable operating expenses and capital expenditure requirements; as well as the risks and uncertainties identified in Entrada's filings with the SEC, including Entrada's most recent Form 10-K and in subsequent filings Entrada may make with the SEC. In addition, the forward- looking statements included in this presentation represent Entrada's views as of the date of this presentation. Entrada anticipates that subsequent events and developments will cause its views to change. However, while Entrada may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing Entrada's views as of any date subsequent to the date of this presentation. January 2026 2
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OUR MISSION: To Treat Devastating Diseases With Intracellular Therapeutics January 2026 3 We’re proud to share the stories of JJ, Andrew, Max and Franklin – all living with Duchenne muscular dystrophy
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d Each target disease has a substantial patient population with a significant unmet medical need An Expanding Pipeline of Intracellular Therapeutics January 2026 Phase 1/2 ENTR-801: USH2A Undisclosed Programs Undisclosed Duchenne Muscular Dystrophy (DMD) Inherited Retinal Diseases Myotonic Dystrophy Type 1 (DM1) – Partnered with ENTR-601-44 ENTR-601-45 ENTR-601-50 ENTR-601-51 VX-670 Preclinical Phase 2/3 4 Pipeline and Platform Expansion
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Building momentum with clinical milestones in 2026 January 2026 *All references in this presentation regarding planned regulatory filings and clinical study designs are subject to ongoing discussion with regulatory authorities; **Based on current operating plans and ~$296M in preliminary unaudited cash, cash equivalents and marketable securities as of December 31, 2025; MAD: Multiple ascending dose; DMD: Duchenne muscular dystrophy; DM1: Myotonic dystrophy type 1. ENTR-601-44 • Cohort 1 dosing complete; Open label dosing initiated • Cohort 1 data expected Q2 and Cohort 2 by year-end 2026 ENTR-601-45 • Cohort 1 data expected mid-2026 ENTR-601-50 • Received authorization for Phase 1/2 MAD study (U.K.) • EU filing expected H2 2026 • Completed SAD portion of global Phase 1/2 study • MAD portion to evaluate safety and efficacy is ongoing • Completion of enrollment and dosing expected in mid-2026 • Partnership terms include milestone payments, plus royalties Inherited Retinal Diseases • Nominated first ocular candidate, ENTR-801 for Usher syndrome type 2A • Second program in lead optimization; Candidate declaration in 2026 Additional Discovery Efforts • Expansion of neuromuscular and ocular franchises • Range of undisclosed diseases and modalities • Ended 2025 with ~$296M cash balance • Cash runway into Q3 2027 Rapidly expanding DMD clinical franchise Vertex accelerating VX-670 for DM1 Advancing innovative preclinical pipeline Strong financial position** 5 Advanced four clinical-stage programs in 2025 with clinical inflection points for ENTR-601-44, ENTR-601-45 and VX-670 expected in 2026
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Neuromuscular Diseases
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Duchenne Muscular Dystrophy (DMD)
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d Entrada is entering 2025 with momentum January 2026 *Accelerated Approval is subject to regulatory feedback; PMO: Phosphorodiamidate morpholino oligomer; EEV: Endosomal Escape Vehicle; HNV: Healthy normal volunteer; PK: Pharmacokinetics; PD: Pharmacodynamics. Entrada’s Duchenne muscular dystrophy strategy Three strategic pillars: Differentiation, de-risking and speed to global approvals • 25-fold improvement in endosomal escape results in best-in-class nonclinical efficacy • Novel PMO sequences are superior to marketed PMOs, even without EEV conjugation • Nonclinical data translated into compelling HNV PK and safety data, supporting the potential for substantial differentiation • Non-linear dose-dependent increases in PK/PD and satellite cell uptake set the platform apart from antibody-based therapies • Drug load compared to antibody-based therapies implies substantially less drug exposure, lower risk of anti-drug antibody response and lower manufacturing burden • Ex-U.S. MAD studies represent an efficient path to clinically meaningful data • Entrada’s neuromuscular programs, including Vertex-partnered VX-670 for DM1, leverage the same EEV • Expected double digit dystrophin production and tolerability from ENTR-601-44 Cohort 1 data will further validate the platform • Positive data in one EEV-enabled candidate immediately derisks the DMD clinical portfolio • The ex-U.S. Phase 1/2 data will be utilized to initiate discussions with FDA regarding U.S. Accelerated Approval* • Opportunity for best-in-class PMO conjugates across portfolio • Opportunity for first-in-class and best-in-class PMO conjugate in the exon 45 skipping population • Accelerated Approval would be expected to coincide with the initiation of global registrational/confirmatory studies to achieve full approval in the U.S. and beyond Differentiated EEV Platform and Novel PMO Conjugate Derisked and Rapid Clinical Development Speed to Global Approval and Commercialization 8
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January 2026 9Qian, Z. et al. ACS Chem. Biol. 2013; Qian, Z. et al. Biochemistry 2014; Qian, Z. et al. Biochemistry 2016; Sahni, A. et al. ACS Chem. Biol. 2020; Pei, D. Acc. Chem. Res. 2022. High Intracellular Uptake ~90% uptake Efficient Endosomal Escape ~25-fold increase in endosomal escape vs. other competitive approaches Unique Budding Mechanism Conserves endosomal integrity Unique chemistry Improved uptake and endosomal escape Cyclic structure Extended half-life and increased stability Phospholipid binding Broad biodistribution to all cells Consistent and predictable pharmacokinetics Same EEV used across DMD and DM1 programs Endosomal Escape Vehicle (EEV )-based therapies for clinical-stage neuromuscular programs
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R6-PMO EEV-PMO 0 10 20 30 40 50 60 70 80 90 100 Exon Skipping (%) * • PMO sequences are the same, cell penetrating peptides are different (linear vs. cyclic) • EEV-PMO significantly improved exon skipping after 3 days in mdx mice as compared to competitive R6-PMO EEV Optimization PMO Optimization • EEVs are the same, PMO sequences are different (casimersen vs. Entrada proprietary) • Proprietary PMO significantly improved exon skipping after 3 days in mdx mice as compared to competitive casimersen sequence January 2026 Entrada optimizes both the EEV delivery vehicle and the active conjugate to create best-in-class medicines 10*p<0.05, **p<0.01, ***p<0.001, ****p<0.0001; relative to saline; Concentrations provided are PMO equivalent; Data presented at 2024 World Muscle Society conference. In the below DMD example, Entrada has optimized the EEV and the PMO sequence; The data represents the superiority of each component against other approaches and sequences Saline EEV-PMO45 (45 mg/kg) ENTR-601-45 (45 mg/kg) 0 10 20 30 40 50 60 70 80 90 100 Exon Skipping (%) ✱✱ ✱✱✱✱ ✱✱✱✱ Casimersen PMO Sequence Proprietary PMO Sequence Casimersen PMO Sequence Proprietary PMO Sequence
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Satellite cell uptake enhances Entrada’s ability to treat a wide range of muscular diseases, starting with DMD January 2026 11 Satellite stem cells are responsible for regenerating and repairing muscles; The ability to access the satellite cells is an important differentiator for EEV therapies D2-mdx mice were treated with 3 IV doses of EEV-PMO administered every six weeks; Gastrocnemius was collected 12 weeks after the third dose and analyzed by immunohistochemistry; Data presented at International Conference on Muscle Wasting 2025; hDMD: Human dystrophin transgene; Q6W: Every 6 weeks. • PMO in satellite cells and newly regenerated muscle fibers create a pool of treated stem cells to improve patients’ regenerative capacity across a range of musculoskeletal diseases • Immunohistochemistry data demonstrates co-localization in hDMD mice ▪ Satellite cells at 7 days ▪ Satellite cells and newly regenerated centrally nucleated fibers 12 weeks post-washout after 3 Q6W doses • Effective regeneration is likely critical to ensuring both near- and long-term functional outcome improvements
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Healthy volunteer safety data is compelling, with no treatment-related AEs reported up to the highest dose January 2026 12 Safety and tolerability were assessed at each study visit following a single IV dose of ENTR-601-44 or placebo; One participant enrolled and randomized into Cohort 3 was removed prior to dosing; Renal biomarkers assessed using the Foundation for the National Institutes of Health (FNIH) and the Critical Path Institute (C-Path) Kidney Safety CM Biomarker User’s Guide, v1.1, 2019; Data presented at 2024 World Muscle Society conference; AE: Adverse event; SAE: Serious adverse event; TEAE: Treatment-emergent adverse event. n (%) Pooled placebo (N=8) ENTR-601-44 0.75 mg/kg (n=6) 1.5 mg/kg (n=6) 3.0 mg/kg (n=7) 6.0 mg/kg (n=6) Total (N=25) Dosed 8 6 6 6 6 24 Completed Study 8 6 6 6 6 24 Any TEAE 1 5 2 3 3 13 Treatment- related TEAE 0 0 0 0 0 0 ENTR-601-44-101 Study design • 32 adults • 6:2 randomization • Single IV dose • 4 cohorts: 0.75, 1.5, 3 and 6 mg/kg Outcome measures • Safety and tolerability • Evaluation of PK and PD • Target engagement as measured via exon skipping ENTR-601-44-101 Phase 1 Study • No AEs related to study drug • Strong clinical safety up to 6 mg/kg Placebo-controlled single ascending dose (SAD) study in healthy volunteers
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Translation of nonclinical data to Phase 1 study establishes transformational potential of Entrada’s DMD therapies January 2026 13 (Left) Blood samples for PK assessment were collected at 2 hours pre-dose and post-end of infusion: 5 minutes, 1 hour, 4 hours, 8 hours, 16 hours, 24 hours and every 24 hours after; Additional samples were taken at follow-up study visits; Muscle concentrations (Center) and exon skipping (Right) were assessed using a needle muscle biopsy taken from biceps brachii 72 hours (±4 hours) post-dose of ENTR-601-44; Box and whisker plot illustration: the boxes represent the IQR and median; Whiskers show the smallest and largest values within 1.5 times the IQR; **p<0.005 vs. placebo using Mann-Whitney U test; Data presented at 2024 World Muscle Society conference; AUClast: Area under the plasma concentration-time curve to the last measurable plasma concentration; IQR: Interquartile range; LLOQ: Lower level of quantification. ENTR-601-44-101 Plasma Concentration ENTR-601-44 Dose (mg/kg) Plasma ENTR-601-44 AUClast (hr*ng/mL) 0 30.75 1.5 6 0 20,000 40,000 60,000 Healthy normal volunteers High drug concentration supports potential for efficacy at relatively low doses Dose-dependent skeletal muscle concentration was observed Robust target engagement with statistically significant exon skipping observed vs. placebo Skeletal Muscle Concentration DMD Exon 44 Skipping 0 20 10 50 40 30 70 60 80 Concentration of final metabolite (ng/g) 6 mg/kg ENTR-601-44 3 mg/kg ENTR-601-44 LLOQ 0.4 0.2 0.0 0.8 0.6 1.0 Exon 44 skipping (%) ** LLOQ Healthy normal volunteers Healthy normal volunteers Superior plasma and muscle exposure as well as positive target engagement at 6 mg/kg with significant exon skipping vs. placebo 6 mg/kg ENTR-601-44 Placebo
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Design Dose Uptake Target engagement Anti-TfR1-mAb-PMO Avidity Anti-TfR1-Fab-PMO Dyne Full-length antibody ~150 kDa Muscle-specific delivery; Extended half-life Fragment antibody ~50 kDa Muscle-specific delivery and rapid uptake Large conjugate doses 5 mg/kg PMO (registrational dose) + ~23 mg/kg mAb = ~28 mg/kg whole drug dose1 Large conjugate doses 20 mg/kg PMO (registrational dose) + undisclosed mg/kg Fab = undisclosed mg/kg whole drug dose2 Apparent limit on dose response No increase in dystrophin from 5 to 10 mg/kg PMO dose in DMD exon 44 patients: 25% vs. 26%4,5 Apparent limit on dose response No increase in dystrophin from 10 to 20 mg/kg PMO dose in DMD exon 51 patients: 2.97% vs. 3.14%2,4 No enhanced endosomal escape Once dissociated from the mAb in the lysosome, the unconjugated PMO escapes at <2% efficiency6 No enhanced endosomal escape Once dissociated from the Fab in the endosome, the unconjugated PMO escapes at <2% efficiency6 EEV therapies are expected to show superior dystrophin production and dose-dependent increases in therapeutic index January 2026 14 1Etxaniz et al., Nucleic Acid Res., 2025; 2Dyne corporate materials from DELIVER Clinical Update investor call September 2025; 3Total mean exon skipping; Entrada internal data from Phase 1 SAD study of ENTR-601-44 in HNV; 4Unadjusted dystrophin, mean change from baseline; 5Avidity corporate materials from Del-zota Topline Data investor call March 2025; 6Dowdy et al., Nucleic Acid Ther., 2022. EEV-PMO Entrada Cyclic, arginine-light peptide 2.6 kDa Tissue-specific delivery; Increases stability and half-life Low conjugate doses ~5 mg/kg PMO + 1 mg/kg EEV = 6 mg/kg whole drug (ELEVATE-44-201 Cohort 1 dose) No limit on dose response seen 48.3% increase in exon skipping from 3 to 6 mg/kg whole drug dose in HNV3 Enhanced endosomal escape ~25-fold increase in endosomal escape vs. other competitive approaches A 25-fold improvement in endosomal escape, novel PMO sequences, non-linear increases in PK/PD, satellite cell uptake and lower whole drug requirements compared to antibody-based therapies
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Preclinical and clinical data together support potential for best-in-class clinical profile for ENTR-601-44 January 2026 15 ENTR-601-44 Entrada PMO: 23 mg/kg Whole dose: 30 mg/kg Avidity PMO: 30 mg/kg Whole dose: ~160 mg/kg • Non-linear increase in exon skipping in NHP • Similar PK curves (in plasma concentrations) between human and NHP1 • For every doubling of dose, there is a more than doubling of metabolite excretion • May imply the potential for increasing efficacy without a proportional risk of increasing toxicity Substantial increase in muscle exposure with less than proportional increase in renal exposure suggests a wide therapeutic index Dystrophin (% of WT) Gastroc Heart 10% 6% Gastroc Heart 46% 6% 7% 4% 2 Weeks Post-Dose 4 Weeks Post-Dose 0 100 200 300 400 500 600 0 10 20 30 40 50 60 5% 10 mg/kg 10% 20 mg/kg 54% 40 mg/kg ENTR-601-44 Dose Exon Skipping (%) Muscle Concentration (ng/g) 100% 100% 100% 114% 130% 184% 0.75 to 1.5 mg/kg 1.5 to 3 mg/kg 3 to 6 mg/kg ENTR-601-44 Dose Change (%) Metabolite Excretion Change (%) 4-7-fold more dystrophin at lower doses than Avidity’s del-zota* Urinary Excretion of Final PMO-44 Metabolite in HNV Non-Linear Dose Response in NHP Del45hDMD.mdx mouse, single dose, cross comparison study* ~ 3x greater muscle concentration in human versus NHP *Comparison with delpacibart zotadirsen (del-zota) is for illustrative purposes only. Entrada internally generated data compared with published data; Etxaniz et al., Nucleic Acids Res. 2025; ; 1Graphs for NHP and HNV plasma concentrations are not at the same doses; Overlaid for illustrative purpose to show similar PK curves; Del45hDMD.mdx: Mouse model used for preclinical evaluation of exon 44 skipping therapies; Novartis to acquire Avidity for $72 per share in cash for total equity value of approximately $12B (October 2025).
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January 2026 16 *Expansion cohort and potential for Accelerated Approval is subject to regulatory feedback; Global registration and approval will require Phase 3 studies to follow the Phase 1/2 studies; Phase 3 studies will likely include functional measures as the primary endpoint (U.S. confirmatory study/EU registrational study); ELEVATE-45-201 protocol is under review and is largely similar to the overall design of ELEVATE-44-201, but with doses starting at 5 mg/kg and escalating up to 15 mg/kg. Screening Double-Blind Period Open Label Period Follow-up Period Up to 6 weeks 19 weeks 31 weeks 6 weeks N=24 patients across three cohorts, n=8 per cohort Within each cohort, randomization 3:1 (ENTR-601-44 to placebo) ✓ Cohort 1: 6 mg/kg or placebo • Cohort 2: ≤12 mg/kg or placebo • Cohort 3: ≤18 mg/kg or placebo x3 doses Days 1, 43 and 85 Muscle biopsy #2 Day 127 Part A Ambulatory patients with DMD who are exon 44 skipping amenable Muscle biopsy #1 Participants who complete Part A are able to continue into Open Label Period • Receive 6 doses of ENTR-601-44 at the level that was administered in participant’s Part A cohort • Dosing initiated • Study blinded to end of Open Label Period Expansion Cohort ELEVATE-44-201 is a global, two-part, randomized, double-blind placebo- controlled Phase 1/2 study in ambulatory patients* Primary objective: Safety and tolerability of ENTR-601-44 Secondary objectives: Evaluation of pharmacokinetics, exon skipping, dystrophin production and measures of function An independent Data Monitoring Committee (DMC) has reviewed initial data from the eight patients enrolled in Cohort 1 and supports continuation without any protocol modifications ELEVATE-44-201 is designed to support U.S. Accelerated Approval and form the basis of a global registrational program*
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ENTR-601-44’s Phase 1 results unlock DMD portfolio investment across multiple populations January 2026 17 EEV therapies have the potential to become best-in-class treatments for DMD; ELEVATE-201 studies are intended to support U.S. Accelerated Approval and form the basis of a global registrational program ENTR-601-44 ENTR-601-45 ENTR-601-51 ENTR-601-50 ELEVATE-50-201 • Received authorization for Phase 1/2 MAD study (U.K.) • EU filing expected H2 2026 • Global study initiation expected by year-end 2026 • Global Phase 1/2 MAD regulatory filings expected 2026 ELEVATE-44-201 • Global Phase 1/2 MAD study ongoing • Cohort 1 dosing complete and Open Label Period dosing initiated • Data from Cohort 1 expected Q2 2026 • Data from Cohort 2 expected by year-end 2026 ELEVATE-44-102 • Intended to support expanded patient populations • Phase 1b MAD study; Initiation expected H1 2026 ELEVATE-45-201 • Global Phase 1/2 MAD study ongoing • Data from Cohort 1 expected mid-2026 45 44 50 51 14% 9% 8% 4% Exon Over 14,000 patients in the U.S. and Europe are within Entrada’s current focus* *Bladen et al., HGVS Journal, January 2015; Crisafulli et al., Orphanet J. Rare Disease, June 2020.
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Myotonic Dystrophy Type 1 (DM1)
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DM1: A transformational partnership with Vertex January 2026 DM1 partnership established with Vertex in Q1 2023 • Entrada received an upfront payment of $224M and an equity investment of$26M upon initiation of the collaboration • Includes up to $485M for the achievement of milestones and tiered royalties on future net sales VX-670 differentiation • Unlike antibody-based approaches, VX-670's targeted and specific blocking of pathogenic CUG repeats drives global transcriptome correction while preserving healthy DMPK levels • Satellite cell uptake may improve outcomes as CUG repeat length correlates with progenitor cell activation, proliferation and differentiation* Vertex advancing placebo-controlled Phase 1/2 clinical program • Completed SAD portion of Phase 1/2 clinical study • MAD portion of study to assess safety and efficacyis ongoing at over 25 global sites • MAD is on track to complete dosing in mid-2026 • Open label extension study is enrolling • Same EEV utilized for VX-670 as in DMD franchise No disease-modifying treatments are currently available for the more than 110,000 people in the U.S. and Europe living with DM1 *Hasuike et al., Front. Genet., March 2022; MBNL: Muscleblind-like proteins; CUG repeat: Repeating sequence of cytosine, uracil and guanine in RNA; DMPK: Dystrophia myotonica protein kinase. 19
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Inherited Retinal Diseases (IRDs)
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Addressing areas of high unmet need in IRDs with new oligonucleotide-based therapeutics January 2026 Usher Syndrome Type 2A (USH2A) • An inherited eye condition caused by changes in the USH2A gene • In some patients, mutations in exon 13 prevent production of the usherin protein • Without usherin, photoreceptors (the light-sensing cells in the eye) gradually degenerate • Lack of usherin leads to vision loss in early adulthood and legal blindness in mid-adulthood • No disease modifying treatments are currently available that can slow or stop disease progression About ENTR-801 • Proprietary exon 13 skipping therapy designed to restore functional usherin protein production with the goal of preserving photoreceptor health and function • Demonstrated robust exon skipping and usherin protein production as well as initial safety in multiple animal models people with Usher syndrome in the U.S. are exon 13 skipping amenable* ~6,500 Entrada’s first IRD clinical candidate, ENTR-801, will target Usher syndrome type 2A *Delmaghani et al., Hum Genet., Apr. 2022; Sanjurjo-Soriano et al., HGG Advance, Oct. 2023; Su et al., Front Aging Neurosci., Aug. 2022. people with Usher syndrome in Europe are exon 13 skipping amenable* ~8,000 21
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ENTR-801: Substantial and durable exon skipping and protein generation January 2026 A single IVT dose of ENTR-801 reaches the exon skipping target expected to be clinically relevant; Protein generation is measurable for at least 90 days suggesting potential for dosing every 2-3 months Duration of Target Engagement in phUSH2A WT Mice Duration of Truncated Usherin Protein Generation in phUSH2A WT Mice Exon skipping target (25%) WB (Left) Partially humanized WT USH2A mice were dosed via single bilateral IVT at multiple concentration for 90-days; Exon skipping evaluated by RT-ddPCR; (Right) Truncated usherin protein was assessed via western immunoblot and quantified via densitometric analysis in image; ddPCR: Double drop PCR; WT: Wild-type; phUSH2A WT: Mouse model used in the evaluation of therapies for USH2A; WB: Western blot. Low Dose High Dose Low Dose High Dose 22
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ENTR-801: A novel exon 13 skipping therapy targeting a subgroup of patients with Usher syndrome type 2A January 2026 ENTR-801 demonstrated robust, dose dependent, exon skipping and usherin protein production as well as initial safety in multiple animal models • ENTR-801 efficacy is dose-dependent and translates to robust usherin protein generation ▪ Following a single injection, ENTR-801 achieved the prespecified target engagement goal of ≥ 25% and usherin protein production lasting 90 days in humanized USH2A mice ▪ Exon skipping was also confirmed in both human iPSC retinal organoids and human retinal explants ▪ Sustained target engagement and long-lived protein supports relatively infrequent and patient-friendly dosing • ENTR-801 is well tolerated at target doses ▪ ENTR-801 was well-tolerated based on in-life observations and confirmed by histopathology* ▪ Lack of off-target risk was addressed via in silico safety evaluation • A second IRD clinical candidate is expected to be named in 2026 • IND-enabling studies will be initiated and clinical strategies will be shared in 2026 iPSC: Induced pluripotent stem cells; *Rabbit established as most sensitive species. 23
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Pipeline Expansion
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Entrada’s flexible and modular platform enables pipeline expansion across therapeutic areas January 2026 25 Selection of future clinical candidates will be modality-agnostic, offer clear differentiation and provide potential for functional cures Complementary modalities tailored to disease-specific requirements • Next-generation EEVs to further enhance therapeutic index with multi-fold improvement in efficacy • Oligonucleotide optimization to develop proprietary sequences with enhanced safety and efficacy, with and without EEV enablement • Candidate optimization to ensure localization to specific intracellular compartments • Protein engineering to improve potency, efficacy and bioavailability Ocular franchise expansion • Undertreated inherited retinal disorders similar to USH2A • Expansion into broader macular degeneration populations Neuromuscular franchise expansion • Candidates that are steric blockers of trinucleotide repeats or knockdown the expression of a specific protein • Delivery of a therapeutic to quiescent satellite cells may drive differentiation by enabling earlier disease intervention Undisclosed • Discovery efforts across a range of diseases and modalities
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Summary
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*All references in this presentation regarding planned regulatory filings and clinical study designs are subject to ongoing discussion with regulatory authorities; **Based on current operating plans and ~$296M in preliminary unaudited cash, cash equivalents and marketable securities as of December 31, 2025. January 2026 27 VX-670 MAD portion of global Phase 1/2 ongoing Multiple 2026 near-term value drivers anticipated across expanding pipeline of intracellular therapeutics ENTR-601-45 Multiple clinical study sites activated in U.K. and EU FPD with Cohort 1 data expected mid-2026 ENTR-601-44 Multiple clinical study sites activated in U.K. and EU FPD with Cohort 1 data expected in Q2 2026 Authorized U.S. study planned for H1 2026 ENTR-601-44 Global Phase 1/2 MAD study ongoing Cohort 1 data expected Q2 2026 and Cohort 2 data by year-end 2026 Authorized U.S. study planned for H1 2026 ENTR-601-45 Global Phase 1/2 MAD study ongoing Cohort 1 data expected mid-2026 VX-670 Completion of MAD patient enrollment and dosing expected in mid-2026 ENTR-601-51 Global Phase 1/2 MAD regulatory filings expected in 2026 Cash runway into Q3 2027 ENTR-601-50 Received authorization for Phase 1/2 MAD study (U.K.) EU filing expected H2 2026 Global study initiation expected by year-end 2026 ENTR-801 Initial IRD candidate focused on Usher syndrome type 2A Additional data and clinical plans will be shared in 2026 Candidate declaration for second IRD program in 2026 Pipeline expansion Next-generation EEVs for neuromuscular expansion Ocular expansion into larger disease areas Range of undisclosed diseases and modalities
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Appendix: Additional DMD Preclinical Data
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Consistent and durable efficacy across species January 2026 29Data presented at the 2022 MDA Clinical and Scientific Conference, TIDES 2022 and OPT 2024. Untreated 3 μM 1 μM 0.3 μM 0.1 μM 0.03 μM 0 20 40 60 80 100 ~40-fold higher ENTR-601-44 Exon 44 Skipping in Healthy and Patient Myoblasts Exon 44 Skipping (%) Healthy cells; n=4 cells/dose Patient cells (DMDΔ45); n=4 cells/dose Exon 44 Skipping (%) Week 1 Week 2 Week 4 Week 8 Week 12 0 20 40 60 80 100 Exon 44 Skipping in hDMD Mouse • Post-IV infusion of single 35 mg/kg (PMO equivalent) dose, robust exon 44 skipping observed in biceps in the ENTR- 601-44 treated NHPs (n=3 per cohort) for at least 12 weeks Pre dose Day 2 Day 7 Day 14 Day 19 Day 28 Day 35 Day 42 Day 56 Day 70 Day 84 0 20 40 60 80 100 • Single 60 mg/kg (PMO equivalent) dose • Tibialis anterior Exon 44 Skipping in NHP Cohort 1 Cohort 2 Exon 44 Skipping (%) ENTR-601-44 Significant potential for patient benefit supported by ENTR-601-44 mouse and NHP data at clinically relevant levels; in vitro data suggest much higher target engagement in patient cells
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January 2026 30*JESS: Automated western blot system; ***EEV conjugated to an exon 44 skipping PMO; Data presented at the 2025 American Society of Gene & Cell Therapy conference. • Del45hDMD.mdx mice dosed with EEV-PMO-44*** • n=4, gastrocnemius sample collection 2 weeks post-injection Dystrophin Restoration* 15 mg/kg 30 mg/kg 60 mg/kg 0 20 40 60 80 100% Dystrophin Restoration Dose Exon Skipping 15 mg/kg 30 mg/kg 60 mg/kg 0 20 40 60 80 100 Dose % Exon 44 Skipping ENTR-601-44 Dose-dependent response at a minimally effective dose of 15 mg/kg is observed, with near saturation at a clinically relevant dose of 60 mg/kg implying a wide therapeutic index Dose-dependent exon skipping and dystrophin
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Preclinical data support potential for best-in-class clinical profile for ENTR-601-45 January 2026 31Data are shown as mean ± SD; *p ≤ 0.05; **p ≤ 0.01; ***p ≤ 0.001; ****p ≤ 0.0001; 25 mg/kg correlates to ~5 mg/kg human equivalent dose (HED), 50 mg/kg correlates to ~10 mg/kg HED, 75 mg/kg correlates to ~15 mg/kg HED; Data presented at the 2024 World Muscle Society conference. • Active and vehicle del44hDMD.mdx mice, n=5 per cohort, EEV-PMO-45 (Q6W x 3 doses); Control saline treated hDMD.mdx mice, n=10 (Q6W x 3 doses) • Skipping (ddPCR) and dystrophin production (JESS) is significantly increased 6 weeks after the third dose of ENTR-601-45 (gastrocnemius muscle shown) Dystrophin RestorationExon Skipping Functional Correction ENTR-601-45 0 20 40 60 80 100% Human Exon 45 Skipping ** **** **** Dose in mg/kg 0 20 40 60 80 100 Dystrophin Restoration (%) Normalized to hDMD.mdx **** *** Dose in mg/kg 0 20 40 60 80 100% Dystrophin Positive Fibers **** **** **** Dose in mg/kg 0 50 100% Force After 10 Contractions **** **** **** *** Dose in mg/kg Dose-dependent increase in exon skipping and dystrophin expression correlates to complete functional correction
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Dose-dependent and durable improvements in muscle function observed in del44hDMD.mdx mice January 2026 32 del44hDMD.mdx mice were treated with three Q6W IV injections of ENTR -601-45 or vehicle; ECC-induced muscle force loss generated by repeated ec centric force (ECC) contraction of the gastrocnemius muscle was assessed 5 weeks (left/center) or 4 and 8 weeks (right) after the third dose; Data (mean ± standard deviation) shown across ten ECC contractions normalized into a percentage of the initial force before any ECC contra ctions and as the percentage of force retained after the tenth contraction; Vehicle -treated hDMD.mdx mice were used as a control group for normal muscle function; One -way ANOVA (Analysis of variance) was used for statistical comp arison to vehicle- treated del44hDMD.mdx mice; **p < 0.01, ***p < 0.001, ****p < 0.0001 vs. vehicle; Data presented at the 2024 World Muscle Society conference. Skeletal Muscle Membrane Stability Stability After Washout ENTR-601-45 Dose-dependent increase in percent force retention following 10 contractions; Increase maintained for at least 8 weeks after the third Q6W dose of ENTR-601-45
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Efficacy of ENTR-601-50 in exon 50 skip amenable mice Single dose of ENTR-601-50 produced robust human DMD exon 50 skipping and dystrophin production; Translated into improvements in muscle function within 2 weeks post-dose ENTR-601-50 Exon Skipping and Dystrophin in the Gastrocnemius Percent Force After 10 Contractions del51hDMD.mdx mice were treated with a single IV injection of ENTR -601-50 or vehicle. Human DMD exon 50 skipping (top) and dystrophin protein expression (bottom) were analyzed in the gastrocnemius, diaphragm and heart 2 weeks post-dose; Percent dystrophin protein restoration is normalized to total protein and normalized to hDMD.mdx controls; Data shown as mean ± standard deviation; One-way ANOVA was used for statistical comparison; ECC - induced muscle force loss generated by repeated ECC contraction of the gastrocnemius muscle was assessed 2 weeks after dosing . Data (mean ± standard deviation) are shown across ten ECC contractions normalized as the percentage of force retained after the tenth contraction; Data presented at the 2025 World Muscle Society conference; IV: Intravenous. January 2026 33 0 50 100 150% Force before injury ✱✱✱✱ ✱✱ ✱✱✱✱ del51hDMD.mdx mice Vehicle 25 45 0 10 20 30 40 Dystrophin restoration (%) Normalized to hDMD. mdx del51hDMD.mdx mice **** Vehicle 25 45 0 20 40 60% Exon 50 Skipping del51hDMD.mdx mice **** **** 45 mg/kg ENTR-601-50 25 mg/kg ENTR-601-50 del51hDMD.mdx vehicle 45 mg/kg ENTR-601-50 25 mg/kg ENTR-601-50 del51hDMD.mdx vehicle *** ENTR-601-50_45 mg/kg ENTR-601-50_25 mg/kg ENTR-601-50_15 mg/kg del51hDMD.mdx vehicle hDMD.mdx vehicle
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