Entrada Therapeutics, Inc. (TRDA)

Overview

We are a clinical-stage biopharmaceutical company aiming to transform the lives of patients by establishing a new class of medicines that engage intracellular targets that have long been considered inaccessible. Through proprietary, versatile and modular approaches, we are advancing a robust development portfolio of genetic medicines for the potential treatment of neuromuscular and inherited retinal diseases, among others. In 2026, we have been actively progressing our ELEVATE-44 and ELEVATE-45 clinical trials. In addition, our VX-670 partnership with Vertex Pharmaceuticals Incorporated ("Vertex") continues to progress, with Vertex on track to share results during the second half of this year. In addition to the ELEVATE-44-201 Cohort 1 results included in this Quarterly Report, we anticipate reporting additional ELEVATE-44-201 Cohort 1 open-label data by the end of 2026 and topline results from the second cohort of our ELEVATE-44-201 trial in the first quarter of 2027. We expect to report our Cohort 1 ELEVATE-45-201 multiple ascending dose ("MAD") data in October 2026. As of June 30, 2026, we had cash, cash equivalents and marketable securities of $223.0 million. Based on our current operating plans, we believe that our cash, cash equivalents and marketable securities as of June 30, 2026 will be sufficient to fund our operations into the third quarter of 2027.

Clinical-Stage Development Pipeline:

Entrada continues to advance multiple clinical programs in people living with Duchenne muscular dystrophy ("DMD") in the United Kingdom ("UK"), European Union ("EU") and United States ("U.S."). In 2026, we have four clinical-stage programs in our DMD franchise (ENTR-601-44, ENTR-601-45, ENTR-601-50 and ENTR-601-51, which has completed IND-enabling studies but has not yet filed a regulatory application). When combined, we estimate that there are over 11,500 patients in the U.S. and Europe that carry mutations amenable to Entrada's current exon skipping programs. Complementing the ongoing clinical progress of the DMD franchise is the myotonic dystrophy type 1 ("DM1") partnership with Vertex ("VX-670"). Each of these programs utilize the same endosomal escape vehicle, and as such, we anticipate initial data readouts from any one of the candidate clinical trials to provide critical insights for the rest.

ELEVATE-44-201: The Company completed Cohort 1 (dosing at 6 mg/kg) of the global Phase 1/2 MAD portion of the clinical study of ENTR-601-44 in ambulatory patients living with DMD who are amenable to exon 44 skipping. Previously announced data from Cohort 1 achieved the primary objective of favorable safety and tolerability, while also demonstrating (post hoc analysis) significant improvements in functional benefit as measured by change in Time to Rise ("TTR") and Time to Rise velocity ("TTRV") from baseline, versus placebo. All eight of the previously-treated and placebo patients have now transitioned to the 6-dose open-label period of the study, which is on track to report data by the end of 2026. A continuation of safety and functional benefit in this portion of the study would strengthen the competitive profile of the program. Enrollment is complete for Cohort 2 of the global Phase 1/2 MAD portion of the study at the increased dose of 12 mg/kg, and we expect to report topline results including safety, exon skipping, dystrophin and functional readouts in the first quarter of 2027. Data from Cohort 3 (up to 18 mg/kg) will follow, if needed. Based on a combination of non-clinical data, healthy volunteer data and Cohort 1 patient data, we anticipate seeing an increase in dystrophin as we increase dosing amounts in the second and third cohorts. We also intend to open an expansion cohort to increase the number of participants treated in the ELEVATE-44-201 study, as this study has been designed to support an accelerated approval in the U.S. Separately, the U.S. Food and Drug Administration ("FDA") granted Rare Pediatric Disease Designation to ENTR-601-44.

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ELEVATE-44-102: The Company believes this clinical trial, in the underserved adult patient population, would be best to initiate at the highest advisable starting dose in patients with advanced disease. Following a review of safety, pharmacokinetic and pharmacodynamic data from Cohort 1 of the ELEVATE-44-201 study in the U.K and EU, we plan to re-engage with the FDA to discuss increasing the planned starting dose in this clinical study. The Company will provide an update on clinical study design and timing following interactions with the FDA.

ELEVATE-45-201: The Company has completed enrollment and dosing of Cohort 1 of the global Phase 1/2 MAD portion of the clinical study of ENTR-601-45 in ambulatory patients living with DMD who are amenable to exon 45 skipping. The Company expects to report data from Cohort 1 (5 mg/kg) in October 2026. All participants from Cohort 1 have transitioned into the open-label, Phase 2 portion of the study. Cohort 2 is dosing at 10 mg/kg and is ongoing. Data from Cohort 2 is expected in the first half of 2027, and data from Cohort 3 (up to 15 mg/kg) will follow, if needed. The proposed ELEVATE-45-201 clinical trial design and dosing regimen is similar to ELEVATE-44-201, incorporating a MAD Phase 1 portion, a 6 dose open-label Phase 2 portion and an expansion cohort. We expect ENTR-601-45 to be both best in class and to be the first PMO-conjugate to generate clinically meaningful data in a population where only low single digit competitive dystrophin production has been observed to date.

ELEVATE-LTE: A Long Term Extension (LTE) platform study protocol (ENTR-DMD-202) was accepted by U.K. and European authorities. This is a phase 2, open-label long-term extension study in participants with Duchenne muscular dystrophy amenable to exon skipping to assess the long-term safety, tolerability, pharmacokinetics, and efficacy of endosomal escape vehicle phosphorodiamidate morpholino oligomer platform products which will enable continued access to drug for study participants while collecting longer-term safety and efficacy data, including functional measures.

ELEVATE-50-201 and ENTR-601-51: We expect to submit additional regulatory applications following a review of data from the ongoing trials of our lead programs. We are evaluating a variety of options to optimize clinical study execution, and we expect to provide more specific timeline guidance as the new strategy is finalized.

VX-670: Vertex has completed enrollment and continues dosing in the MAD portion of the GALILEO global Phase 1/2 clinical trial of VX-670 in people with DM1. The study is assessing safety and preliminary efficacy, including change from baseline in the splicing index and other endpoints evaluating muscle function and strength. Vertex is on track to complete dosing and report results in the second half of 2026.

Expanding Preclinical Pipeline:

The Company has advanced two ocular programs into lead optimization for the potential treatment of inherited retinal diseases. Both programs are novel oligonucleotide-based therapeutics with the potential to address areas of high unmet need. In December 2025, Entrada announced its first ocular clinical candidate, ENTR-801, for the potential treatment of Usher syndrome type 2A ("USH2A"). The Company plans to announce a second clinical candidate in ocular diseases in the second half of 2026 and continues to explore novel targets to address both rare and more common retinal conditions. From a strategic point of view, progress in a new therapeutic area enables portfolio diversification in the form of tissue type, route of administration and regulatory pathway. At the same time, however, as in our neuromuscular franchise, initial targets are selected based on well-understood biology, significant unmet need, translational clarity and the potential to differentiate based on our proprietary technologies and capabilities.

ENTR-801: The Company's first ocular candidate is an optimized, proprietary oligonucleotide-based therapy for the potential treatment of a subgroup of patients with USH2A, who are amenable to exon 13 skipping. The clinical candidate was designed to restore functional usherin protein production with the goal of preserving photoreceptors (the light-sensing cells in the eye) to stabilize the overall retinal architecture and preserve function. ENTR-801 was selected from a library of 200 sequences based on its robust exon skipping and usherin protein production, as well as initial safety data in multiple animal models.

We continue to believe that the robust supporting data and ongoing progress of our growing portfolio of clinical and preclinical candidates has the potential to make a significant difference in the lives of patients.

ENTR-601-44-201 (ELEVATE-44-201) Phase 1/2 Cohort 1 Results

Clinical Trial Overview

ELEVATE-44-201 is a global, two-part, randomized, double-blind, placebo-controlled Phase 1/2 study evaluating the safety, tolerability and effectiveness of ENTR-601-44 in ambulatory participants ages four to twenty with DMD who

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are exon 44 skipping amenable. The multiple ascending dose Part A portion of the study is evaluating the safety, pharmacokinetics, pharmacodynamics and functional parameters following intravenous administration of ENTR-601-44 to study participants in three cohorts at sites in the U.K. and EU. The MAD portion of the study enrolled eight participants with DMD in Cohort 1. They were randomized 3:1 to receive ENTR-601-44 at a dose of 6 mg/kg or placebo, administered intravenously. During this double-blind period, doses were administered on days one, 43 and 85, and muscle biopsies were performed at the time of screening and at six weeks after the last dose. Following the initial three doses administered in Part A, all participants continued into the Phase 2, open-label portion in which the safety and efficacy of ENTR-601-44 are evaluated over a longer period of time.

Summary of Demographics and Baseline Patient Characteristics

The average age of treated participants in Cohort 1 was 9.3 years old with a mean age of disease onset of 2.2 years. Per protocol, all participants were ambulatory and all were on a stable dose of steroids. Baseline dystrophin in both the placebo and treatment population was also lower than that reported in competitive exon 44 skipping clinical trials. This is notable as treatment response is generally considered to correlate with higher baseline dystrophin levels.

Safety and Tolerability Data

Cohort 1 achieved its primary endpoint, demonstrating a generally favorable safety and tolerability profile. All treatment emergent adverse events (TEAEs) were mild to moderate. There were no discontinuations and no serious adverse events reported. The most common adverse event (AE) seen was headache.

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Importantly, clinically relevant markers of kidney function including eGFR, Cystatin-C and magnesium were all within normal ranges and treated subjects were comparable to placebo. Participant level data is presented below.

We believe these results to be encouraging, given that the kidney has historically been the organ of toxicity concern for PMO-based oligonucleotides and peptide conjugates in particular, and because similarly favorable safety was observed at 6 mg/kg in the Phase 1 healthy normal volunteer trial disclosed in 2024.

Biodistribution and Biomarkers

Lower than expected plasma Cmax and AUC (area under the curve) was observed in the ENTR-601-44-201 pediatric DMD patient study when compared with our prior ENTR-601-44-101 Phase 1 healthy adult volunteer study. Our current understanding is that this difference is due to a combination of age and disease status, and that higher doses of drug may result in higher levels of drug concentration in circulation. This lower than expected drug concentration, along with lower than expected baseline dystrophin value

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Item 7. MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS

You should read the following discussion and analysis of our financial condition and results of operations together with our consolidated financial statements and related notes appearing elsewhere in this Annual Report on Form 10-K (“Annual Report”). Some of the information contained in this discussion and analysis or set forth elsewhere in this Annual Report, including information with respect to our plans and strategy for our business, includes forward-looking statements that involve risks and uncertainties. As a result of many factors, including those factors set forth in the “Risk Factors” section of this Annual Report, our actual results could differ materially from the results described in, or implied by, the forward-looking statements contained in the following discussion and analysis. You should carefully read the “Cautionary Note Regarding Forward Looking Statements” and “Risk Factors” sections of this Annual Report to gain an understanding of the important factors that could cause actual results to differ materially from our forward-looking statements contained in the following discussion and analysis.

Overview

We are a clinical-stage biopharmaceutical company aiming to transform the lives of patients by establishing a new class of medicines that engage intracellular targets that have long been considered inaccessible. Through proprietary,

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versatile and modular approaches, we are advancing a robust development portfolio of genetic medicines for the potential treatment of neuromuscular and inherited retinal diseases, among others. In 2026, we expect to progress our ENTR-601-44 and ENTR-601-45 clinical trials, an EU filing for the ENTR-601-50 clinical trial, and regulatory submissions for ENTR-601-51. In addition, our VX-670 partnership with Vertex Pharmaceuticals Incorporated (“Vertex”) continues to progress, with dosing completion anticipated in mid-2026. We anticipate reporting on the results of two cohorts of patient data from our ENTR-601-44 program, and one from our ENTR-601-45 program during 2026. As of December 31, 2025, we had cash, cash equivalents and marketable securities of $295.7 million. Based on our current operating plans, we believe that our cash, cash equivalents and marketable securities as of December 31, 2025 will be sufficient to fund our operations into the third quarter of 2027.

Components of Our Results of Operations

Revenue

Substantially all of our revenue to date has been derived from the Vertex Agreement. We do not expect to generate any revenue from the sale of products unless and until such time that our product candidates have advanced through clinical development and regulatory approval, if ever. If our development efforts for our therapeutic candidates are successful and result in regulatory approval or we successfully enter into collaboration or license arrangements with third parties, we may generate revenue in the future from product sales, payments from collaboration or license arrangements including those that we may enter into with third parties, or any combination thereof.

Operating Expenses

Research and Development Expenses

Research and development expenses consist primarily of costs incurred for our research activities, including our discovery efforts, and the development of our programs. These expenses include:

•personnel-related expenses, including salaries, related benefits and stock-based compensation expense for individuals engaged in research and development functions;

•expenses incurred in connection with our research programs and development of our therapeutic candidates and research programs, including under agreements with third parties, such as consultants, contractors and CROs to conduct preclinical studies and clinical trials;

•the cost of developing and validating our manufacturing process for use in our preclinical studies and potential future clinical trials, including the cost of raw materials used in our research and development activities and engaging with third party CMOs;

•costs incurred in connection with the performance of research and development activities under the Vertex Agreement;

•the cost of laboratory supplies and research materials;

•the costs of payments made under third-party licensing agreements and related future payments should certain development and regulatory milestones be achieved; and

•facilities, depreciation and other direct and allocated expenses, including rent and other operating costs, incurred as a result of our research and development activities.

We expense research and development costs as incurred. Non-refundable advance payments that we make for goods or services to be received in the future for use in research and development activities are recorded as prepaid expenses. The prepaid amounts are expensed as the related goods are delivered or the services are performed, or when it is no longer expected that the goods will be delivered or the services rendered. Upfront payments under license agreements are expensed upon receipt of the license and annual maintenance fees under license agreements are expensed in the period in which they are incurred. Milestone payments under license agreements are accrued, with a corresponding expense being recognized, in the period in which the milestone is determined to be probable of achievement and the related amount is reasonably estimable.

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Our research and development costs are primarily devoted to supporting our neuromuscular program development and platform discovery efforts. Our direct external research and development expenses consist primarily of fees paid to outside consultants, CROs, CMOs and research laboratories in connection with our process development, manufacturing and clinical development activities. Our direct external research and development expenses also include fees incurred under license and intellectual property purchase agreements. We track these external research and development costs on a program-by-program basis as we identify specific programs and product candidates to advance into clinical development.

We do not allocate employee costs, costs associated with our development efforts and facilities, including depreciation or other indirect costs, to specific programs because these costs are deployed across multiple programs and, as such, are not separately classified. We use internal resources and third-party consultants primarily to conduct our research and development activities as well as for managing our process development, manufacturing and clinical development activities.

Therapeutic candidates in later stages of clinical development generally have higher development costs than those in earlier stages of clinical development, primarily due to the increased size and duration of later-stage clinical trials. We expect that our research and development expenses will increase substantially in connection with our platform development efforts and planned preclinical and clinical development activities in the near term and in the future. We expect that the research and development expenses of our programs will increase in the near term as we initiate and conduct clinical trials as well as investigational new drug (CTA/IND)-enabling activities for our therapeutic candidates. Therefore, we cannot reasonably estimate or know the nature, timing, and costs of the efforts that will be necessary to complete the preclinical and clinical development of any of our therapeutic candidates. The successful development of our therapeutic candidates is highly uncertain. This is due to the numerous risks and uncertainties associated with product development, including the following:

•the scope, timing, rate of progress and expenses of our ongoing and potential future research activities, including preclinical and IND-enabling studies, clinical trials and other research and development activities we decide to pursue;

•the successful initiation, enrollment and completion of clinical trials under current good clinical practices;

•the timing of filing and acceptance of INDs or comparable foreign applications that allow commencement of future clinical trials for our therapeutic candidates;

•whether our therapeutic candidates show safety and efficacy in our clinical trials and an acceptable risk-benefit profile in the intended populations;

•our ability to hire and retain key research and development personnel;

•our ability to successfully develop, obtain regulatory and marketing approvals of our therapeutic candidates for the expected indications and patient populations;

•our ability to establish and maintain agreements with third-party manufacturers for clinical supply for our clinical trials and commercial manufacturing, if our therapeutic candidates are approved;

•commercializing therapeutic candidates, if and when approved, whether alone or in collaboration with others;

•our ability to maintain a continued acceptable safety, tolerability and efficacy profile of our therapeutic candidates following approval;

•our ability to establish new licensing or collaboration arrangements to support our potential therapeutic candidates on favorable business terms;

•any decisions we make to discontinue, delay or modify our programs to focus on others;

•obtaining, maintaining, protecting and enforcing patent and trade secret protection and regulatory exclusivity for our therapeutic candidates; and

•obtaining and maintaining adequate coverage and reimbursement from third party payors.

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A change in the outcome of any of these variables with respect to the development of any of our therapeutic candidates could significantly change the costs and timing associated with the development of that therapeutic candidate. We may never succeed in obtaining regulatory approval for any of our therapeutic candidates.

General and Administrative Expenses

General and administrative expenses consist primarily of salaries and personnel-related costs, including stock-based compensation, for our personnel in executive, legal, finance and accounting, corporate and business development, human resources and other administrative functions. General and administrative expenses also include: legal fees relating to intellectual property and corporate matters; professional fees paid for accounting, auditing, consulting and tax services; insurance costs; travel expenses; information technology expenses; and facility costs not otherwise included in research and development expenses.

We anticipate that our general and administrative expenses will increase in the future as we increase our headcount and expand our facilities to support our continued research activities and development of our programs and EEV Platform. We also anticipate that we will incur increased accounting, audit, legal, regulatory, compliance, director and officer insurance and investor and public relations expenses associated with operating as a public company.

Interest and Other Income

Interest and other income (expense) consists primarily of interest earned on our invested cash equivalents and marketable securities.

Income Taxes

The Company recorded income tax expense of $0.9 million for both the year ended December 31, 2025 and the year ended December 31, 2024. The income tax expense recorded for the year ended December 31, 2025 was primarily driven by adjustments made upon the finalization of tax returns. The income tax expense recorded for the year ended December 31, 2024 was primarily driven by the current tax liability associated with the $75.0 million payment for the achievement of the clinical advancement milestone for VX-670 and $1.7 million in related interest owed to taxing authorities pursuant to Section 453A. For additional details about the current year tax provision, refer to Note 9, Inco

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