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Entrada Therapeutics Inc

For the period ended Dec 31, 2024. Filed Feb 27, 2025.

View on SEC.gov

About this filing

A company's yearly report to the SEC, with audited financial statements. It is the fullest account a company gives of its business, its finances and the risks it sees.

FY2024 · Filed Feb 27, 2025

TRDA$4.89+7.5%Stored close · as of Nov 6, 2026

What changed in Management’s Discussion and Analysis?

Read the current filing

Previous report: 10-K

Period ended 2023-12-31; filed 2024-03-13.

0001689375-24-000016

Item 7.

Current report: 10-K

Period ended 2024-12-31; filed 2025-02-27.

0001689375-25-000011

Item 7.

The baseline is this issuer’s latest earlier reporting period of the same form that was filed before the current report. A previous 10-Q is a different quarter, not a year-over-year comparison. Amendments are excluded.

Compared 148 previous paragraphs and 146 current paragraphs.

96 unchanged; 35 reworded; 14 added; 16 removed; 1 previous and 1 current paragraphs rearranged.

Tables are not compared: 3 previous and 3 current tables excluded. Dates, whitespace, punctuation and numbering changes are ignored; changes to financial figures remain significant.

A changed paragraph is not evidence that risk increased or decreased. An unchanged paragraph does not establish that risk stayed the same.

Added paragraphs (14)

Current report

We are a clinical-stage biopharmaceutical company aiming to transform the lives of patients by establishing a new class of medicines which engage intracellular targets that have long been considered inaccessible. We enter 2025 with significant momentum, including the planned initiation of our next clinical trial of ENTR-601-44, regulatory submissions under review for ENTR-601-45, and the ongoing progress of our VX-670 partnership with Vertex Pharmaceuticals Incorporated (“Vertex”). We plan to have four clinical programs in patients ongoing by the end of 2025, marking a new phase in the Company’s growth. This regulatory progress follows positive preliminary data in healthy volunteers from a Phase 1 clinical trial, ENTR-601-44-101, reported in 2024.

Current report

Key business updates include:

Current report

•In 2024, we submitted regulatory applications to initiate global Phase 1/2 MAD clinical studies in patients for ENTR-601-44 in the United States, United Kingdom and Europe. We have also submitted regulatory applications to initiate a Phase 1/2 MAD clinical study of ENTR-601-45 in the United Kingdom and Europe for patients living with DMD who are amenable to exon 45 skipping.

Current report

•On February 3, 2025, we announced the receipt of authorization from the United Kingdom’s Medicines and Healthcare Products Regulatory Agency (“MHRA”) and Research Ethics Committee for its Clinical Trial of an Investigational Medicinal Product to initiate ELEVATE-44-201, a Phase 1/2 multiple ascending dose (“MAD”) clinical study of ENTR-601-44 for the potential treatment of Duchenne muscular dystrophy (“Duchenne” or “DMD”) in patients with a confirmed mutation in the DMD gene amenable to exon 44 skipping. We are on track to initiate ELEVATE-44-201 in the United Kingdom in the second quarter of 2025.

Current report

•On February 24, 2025, we announced that the United States Food and Drug Administration (“FDA”) had lifted the clinical hold on the Investigational New Drug application (“IND”) for ENTR-601-44, and we received authorization to initiate ELEVATE-44-102, a Phase 1b MAD clinical study of ENTR-601-44 in adult DMD patients. The Company plans to initiate study enrollment in the first half of 2026.

Current report

•Based on the positive preclinical data, we are on track to submit regulatory applications to initiate a clinical trial of our third Duchenne product candidate, ENTR-601-50, in patients who are exon 50 skipping amenable, in the fourth quarter of 2025.

Current report

•In 2024, we selected ENTR-601-51 as our clinical candidate for our exon 51 program in patients who are exon 51 skipping amenable, and expect to submit global regulatory filings in 2026.

Current report

•Our Vertex partnered candidate, VX-670, is in an ongoing global Phase 1/2 clinical trial, and in November 2024, Vertex announced completion of the Phase 1 SAD portion of the study and initiation of the Phase 2 MAD portion to evaluate both safety and efficacy.

Current report

•We have also generated positive preclinical data from programs outside of our neuromuscular franchise, which include new moieties, and expect to share our first clinical candidate in ocular disease later in 2025.

Current report

•CROs in connection with the ELEVATE clinical studies; and

Current report

•an increase of$10.8 million in direct research and development costs primarily driven by additional activities performed to advance our DMD programs and discovery work for future product candidates;

Current report

•an increase of$4.1 million in facility related and other costs to support our expanding operations.

Current report

In June 2024, we entered into a securities purchase agreement with a limited number of investors relating to a registered direct offering (the “June 2024 Offering”) of 3,367,003 shares of our common stock at a purchase price of $14.85 per share and, in lieu of common stock to certain investors who so chose, pre-funded warrants (the “Pre-Funded Warrants”) to purchase 3,367,003 shares of our common stock at a purchase price of $14.8499 per Pre-Funded Warrant, which represents the price per share at which the shares of common stock were sold to the investors in the June 2024 Offering, minus $0.0001, which is the exercise price of each Pre-Funded Warrant. The June 2024 Offering was made pursuant to the shelf registration statement on Form S-3 (File No. 333-268099) previously filed with the SEC on November 1, 2022 and declared effective by the SEC on November 7, 2022. The aggregate net proceeds from the sale of common stock and Pre-Funded Warrants in the June 2024 Offering were approximately $99.6 million, after deducting offering expenses payable by us. We will receive nominal proceeds, if any, from the exercise of the Pre-Funded Warrants.

Current report

Based on the market value of our common stock held by our non-affiliates as of the last business day of the fiscal quarter ended June 30, 2024, we no longer qualify as a “smaller reporting company” as defined in the Exchange Act, effective December 31, 2024. Therefore, beginning with our Quarterly Report on Form 10-Q for the fiscal quarter ending March 31, 2025, we will no longer be eligible to rely on the reduced disclosure and reporting requirements applicable to smaller reporting companies, while still applying the scaled disclosure requirements for smaller reporting companies in this Annual Report.
Removed paragraphs (16)

Previous report

Our most advanced therapeutic candidate, ENTR-601-44, is being developed for patients with DMD that are exon 44 skipping amenable. On July 24, 2023, we received authorization from the MHRA for our Phase 1 clinical trial in healthy volunteers, ENTR-601-44-101. The Phase 1 clinical trial's primary objective is to evaluate the safety and tolerability of a single dose of ENTR-601-44 in healthy volunteers, with a target enrollment of approximately 40 participants. The trial will also evaluate pharmacokinetics and target engagement as measured by exon skipping in the skeletal muscle, bearing the Company's recentin vitro data showed that exon skipping was approximately 10-40x higher in dystrophic muscle compared to healthy muscle, suggesting that data from healthy normal volunteers may substantially underestimate potential potency. On March 13, 2024, we announced that the first, second and third cohorts of participants had been successfully dosed and we expect to report data from the Phase 1 clinical trial in the second half of 2024. The data from this trial will inform our global clinical development strategy, and if favorable, support regulatory filings to open a global multiple ascending dose (MAD) Phase 2 trial in the fourth quarter of 2024. It is expected that countries will be included in the trial on a rolling basis, as dependent on discussions with individual regulators.

Previous report

On December 19, 2022, we announced that we received a clinical hold notice from the FDA regarding the IND application for ENTR-601-44. The FDA has requested that we continue to gather and submit additional information regarding ENTR-601-44 and we are actively working to resolve the clinical hold in the United States.

Previous report

On January 9, 2023, we announced the selection of a second clinical candidate within our Duchenne franchise, ENTR-601-45, for the potential treatment of people living with DMD who are exon 45 skipping amenable. We plan to submit a CTA/IND application for ENTR-601-45 in the fourth quarter of 2024.

Previous report

On November 7, 2023, we announced the selection of a third clinical candidate within our Duchenne franchise, ENTR-601-50, for the potential treatment of people living with DMD who are exon 50 skipping amenable. The selection of ENTR-501-50 is based onin vivo preclinical data that demonstrated robust exon 50 skipping across cardiac and skeletal muscle groups. We plan to submit a CTA/IND application for ENTR-601-50 in 2025.

Previous report

We have also entered into a Strategic Collaboration and License Agreement, which was amended in October 2023, (the Vertex Agreement) with Vertex Pharmaceuticals Incorporated (Vertex) pursuant to which we granted Vertex an exclusive worldwide license to research, develop, manufacture and commercialize VX-670, our intracellular EEV-based therapeutic candidate for the treatment of myotonic dystrophy type 1 (DM1) that targets expanded CUG repeats in DM1 protein kinase (DMPK) mRNA transcripts, as well as any additional EEV-based therapeutic candidates that may be identified by the Company for the potential treatment of DM1 in the course of the parties’ global research collaboration. The Vertex Agreement provides for a four-year global research collaboration under which Vertex will fund our continued preclinical development of VX-670, as well as the option to fund additional DM1-related research activities with a goal of identifying other EEV-based therapeutic product candidates for the potential treatment of DM1. Other than our efforts under this research collaboration, Vertex will be responsible for global development, manufacturing and commercialization of the licensed products.

Previous report

Under the terms of the Vertex Agreement, Entrada received $250.0 million from the Vertex agreement comprised of an upfront payment of $223.7 million and an equity investment of $26.3 million in our common stock at $16.26 per share. In October 2023, the Company achieved a milestone pursuant to the Vertex Agreement related to preclinical IND-enabling GLP toxicology studies of VX-670 that triggered a $17.5 million milestone payment, which the Company received in November 2023.

Previous report

On January 7, 2024 Vertex announced authorization from the MHRA of a clinical trial application for VX-670 for patients with DM1 and initiation of a Phase 1/2 clinical trial in patients with DM1 in Canada and that it will initiate the study in the UK in the near-term. Vertex also noted that they submitted an IND application to the FDA for VX-670. The FDA requested additional information, which resulted in a clinical hold. Vertex is working to address the FDA's comments in order to initiate the study in the U.S.

Previous report

On July 31, 2023 we entered into a license agreement to advance the development of ENTR-501 with Pierrepont Therapeutics, Inc., a mitochondrial disease-focused company. ENTR-501 is an intracellular thymidine phosphorylase enzyme replacement therapy in development for the treatment of mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). MNGIE is a slowly progressive, but fatal, disease characterized by elevated levels of thymidine. Preliminary preclinical studies have demonstrated that ENTR-501 reduces toxic thymidine levels below those observed in wild-type mice. Pharmacokinetic and acute and chronic toxicology studies indicated both a long circulating half-life and a favorable tolerability profile. We continue to believe that the program will have an important role to play in the future treatment of patients with MNGIE.

Previous report

•the timing and likelihood of resolution of the clinical hold on our IND application for ENTR-601-44 and initiation of clinical trials for ENTR-601-44 in the United States;

Previous report

•the effects of worldwide pandemics and health crises.

Previous report

Subsequent to the IPO, the fair value of the common stock underlying our stock-based awards is the closing price of our common stock on the date of grant.

Previous report

(1)Prior year amounts for collaboration services relate to research and development costs incurred for VX-670 prior to entering into the Vertex Agreement.

Previous report

•an increase of$13.7 million in external costs primarily driven by higher costs incurred as we advance our preclinical activities for our ENTR-601-45 and other preclinical and discovery programs.

Previous report

•a $1.3 million decrease in professional services costs;

Previous report

•a $0.4 million increase in facility and equipment-related expenses in connection with the operating lease for our corporate headquarters; and

Previous report

We are also a “smaller reporting company,” meaning that the market value of our stock held by non-affiliates is less than $700 million and our annual revenue was less than $100 million during the most recently completed fiscal year. We may continue to be a smaller reporting company if either (i) the market value of our stock held by non-affiliates is less than $250 million or (ii) our annual revenue was less than $100 million during the most recently completed fiscal year and the market value of our stock held by non-affiliates is less than $700 million. If we are a smaller reporting company at the time we cease to be an emerging growth company, we may continue to rely on exemptions from certain disclosure requirements that are available to smaller reporting companies. Specifically, as a smaller reporting company we may choose to present only the two most recent fiscal years of audited financial statements in our Annual Report on Form 10-K and, similar to emerging growth companies, smaller reporting companies have reduced disclosure obligations regarding executive compensation.
Reworded paragraphs (35)

Previous wording

We are a clinical-stage biopharmaceutical company aiming to transform the lives of patients by establishing a new class of medicines which engage intracellular targets that have long been considered inaccessible. The Company’s Endosomal Escape Vehicle (EEV™)-therapeutics are designed to enable the efficient delivery of a wide range of therapeutics into a variety of organs and tissues, resulting in an improved therapeutic index. Through our proprietary, highly versatile and modular EEV platform (EEV Platform), we are building a robust development portfolio of therapeutic candidates. Our first two drug candidates are in clinical trials, and we expect to initiate additional regulatory filings by the end of 2024. We believe that the potential success of our early programs can translate into the efficient development of additional EEV therapeutic candidates and allow us to build portfolios in neuromuscular disease and beyond.

Current wording

We believe that the potential success of our early programs can translate into the efficient development of additional therapeutic candidates and allow us to build portfolios in neuromuscular disease and beyond.

Previous wording

Since our inception, we have devoted substantially all our resources to research and development efforts relating to our EEV Platform, advancing development of our portfolio of programs and general and administrative support for these operations, including raising capital. Since our inception, we have raised over $650.0 million of gross proceeds from sales of stock to leading biotechnology investors and from the Vertex Agreement.

Current wording

Since our inception, we have devoted substantially all our resources to research and development efforts relating to our EEV Platform, advancing development of our portfolio of programs and general and administrative support for these operations, including raising capital. We have raised over $850.0 million of gross proceeds from equity sales to leading biotechnology investors and from the Vertex Agreement.

Previous wording

Since inception, we have incurred significant net losses. As of December 31, 2023, we had an accumulated deficit of $195.0 million. We expect to continue to generate operating losses and negative operating cash flows for the foreseeable future as we advance our platform and EEV therapeutic candidates. We will not generate any revenue from product sales unless and until we successfully complete clinical development and obtain regulatory approval for one or more therapeutic candidates, if ever. If we obtain regulatory approval for any therapeutic candidates, we expect to incur significant expenses related to developing our internal commercialization capability to support product sales, marketing and distribution.

Current wording

Since inception, we have incurred significant net losses. As of December 31, 2024, we had an accumulated deficit of $129.3 million. We expect to generate operating losses and negative operating cash flows for the foreseeable future as we advance our platform and EEV therapeutic candidates. We will not generate any revenue from product sales unless and until we successfully complete clinical development and obtain regulatory approval for one or more therapeutic candidates, if ever. If we obtain regulatory approval for any therapeutic candidates, we expect to incur significant expenses related to developing our internal commercialization capability to support product sales, marketing and distribution.

Previous wording

Furthermore, we expect to incur additional costs associated with operating as a public company, including significant legal, accounting, investor relations and other expenses. As a result, we will need substantial additional funding to support our continuing operations and pursue our growth strategy, as we advance therapeutic candidates through preclinical and, if successful, into clinical development, seek regulatory approval, prepare for and, if any therapeutic candidates are approved, proceed to commercialization and operate as a public company. Until such time as we can generate significant revenue from product sales, if ever, we expect to finance our operations through the sale of equity, debt financings or other capital sources, including potential collaborations with other companies or other strategic transactions.

Current wording

Furthermore, we expect to continue to incur additional costs associated with operating as a public company, including significant legal, accounting, investor relations and other expenses. As a result, we will need substantial additional funding to support our continuing operations and pursue our growth strategy, as we advance therapeutic candidates through preclinical and, if successful, into clinical development, seek regulatory approval, prepare for and, if any therapeutic candidates are approved, proceed to commercialization and operate as a public company. Until such time as we can generate significant revenue from product sales, if ever, we expect to finance our operations through the sale of equity, debt financings or other capital sources, including potential collaborations with other companies or other strategic transactions.

Previous wording

As of December 31, 2023, we had cash, cash equivalents and marketable securities of$352.0 million. We believe that our cash, cash equivalents and marketable securities as of December 31, 2023, together with ongoing research support and the anticipated achievement of certain milestones under the Vertex Agreement will be sufficient to extend our cash runway through the second quarter of 2026, supporting the Company's expansion and continued development of EEV therapeutic candidates targeting Duchenne muscular dystrophy and advance EEV-therapeutic candidates in indications beyond neuromuscular disease. We have based this estimate on assumptions that may prove to be wrong, and we could exhaust our available capital resources sooner than we expect. See “Management’s Discussion and Analysis of Financial Condition and Results of Operations—Liquidity and Capital Resources.” To finance our operations beyond that point we will need to raise additional capital, which cannot be assured.

Current wording

As of December 31, 2024, we had cash, cash equivalents and marketable securities of$420.0 million. Based on our current operating plans, we believe that our cash, cash equivalents and marketable securities as of December 31, 2024 will be sufficient to fund our operations into the second quarter of 2027. We have based this estimate on assumptions that may prove to be wrong, and we could exhaust our available capital resources sooner than we expect. See “Management’s Discussion and Analysis of Financial Condition and Results of Operations—Liquidity and Capital Resources.” To finance our operations beyond that point we will need to raise additional capital, which cannot be assured.

Previous wording

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.

Current wording

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.

Previous wording

•expenses incurred in connection with the discovery and preclinical development of our therapeutic candidates and research programs, including under agreements with third parties, such as consultants, contractors and CROs;

Current wording

•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;

Previous wording

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 expect to 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.

Current wording

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.

Previous wording

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

Current wording

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

Previous wording

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

Current wording

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

Previous wording

The Company recorded an income tax expense of$18.7 million for the year ended December 31, 2023. The income tax expense was driven largely by the current tax liability associated with the tax recognition of the Vertex Agreement payments received during 2023. The Company reported no income tax expense for the year ended December 31, 2022.

Current wording

The Company recorded income tax expense of$0.9 million for the year ended December 31, 2024 and income tax expense of$18.7 million for theyear ended December 31, 2023. The income tax expense recorded for the year ended

Previous wording

The Company recorded income tax expense of$18.7 million for the year ended December 31, 2023. The income tax expense recorded was driven largely by the current tax liability associated with the tax recognition of the Vertex Agreement payments received during 2023. A significant portion of the taxable income related to the collaboration payment is offset by current year expenses and prior year accumulated losses. For additional details about the current year tax provision, refer to Note 9, Income Taxes, to the Consolidated Financial Statements appearing elsewhere in this Annual Report on Form 10-K.

Current wording

December 31, 2024 was driven largely 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. The income tax expense recorded for the year ended December 31, 2023 was driven largely by the current tax liability associated with the tax recognition of the upfront payment received pursuant to the Vertex Agreement and the capitalization of research and development expenses under Section 174. For both periods, a significant portion of the taxable income related to the collaboration payments was offset by current year expenses and prior year accumulated losses. For additional details about the current year tax provision, refer to Note 9, Income Taxes, to the Consolidated Financial Statements appearing elsewhere in this Annual Report on Form 10-K.

Previous wording

As of December 31, 2023, we had federal net operating loss carryforwards of$14.6 million, which may be available to offset future taxable income. None of our federal net operating loss carryforwards will expire, but all are limited in their usage to an annual deduction equal to 80% of annual taxable income. In addition, as of December 31, 2023, we had state net operating loss carryforwards of$8.7 million, which may be available to offset future taxable income and expire at various dates beginning in 2036. As of December 31, 2023, we also had federal and state research and development tax credit carryforwards of$2.1 million and$0.8 million, respectively, which may be available to reduce future tax liabilities and expire at various dates beginning in 2039 and 2035, respectively.

Current wording

As of December 31, 2024, we had federal net operating loss carryforwards of$4.2 million, which may be available to offset future taxable income. None of our federal net operating loss carryforwards will expire, but all are limited in their usage to an annual deduction equal to 80% of annual taxable income. In addition, as of December 31, 2024, we had state net operating loss carryforwards of$6.0 million, which may be available to offset future taxable income and expire at various dates beginning in 2036. As of December 31, 2024, we also had federal and state research and development tax credit carryforwards of$3.4 million and$1.5 million, respectively, which may be available to reduce future tax liabilities and expire at various dates beginning in 2039 and 2035, respectively.

Previous wording

All of our revenue to date has been generated from the Vertex Agreement. We account for revenue pursuant to ASC Topic 606, "Revenue from Contracts with Customers" (ASC 606). For additional details regarding our associated accounting policies of ASC 606, refer to Notes 2, Summary of Significant Accounting Policies, and 12, Collaboration and License Agreements, to the consolidated financial statements appearing elsewhere in this Annual Report on Form 10-K.

Current wording

Substantially all of our revenue to date has been generated from the Vertex Agreement. We account for revenue pursuant to ASC Topic 606, "Revenue from Contracts with Customers" ("ASC 606"). For additional details regarding our associated accounting policies of ASC 606, refer to Notes 2, Summary of Significant Accounting Policies, and 12, Collaboration and License Agreements, to the consolidated financial statements appearing elsewhere in this Annual Report on Form 10-K.

Previous wording

As part of the process of preparing our consolidated financial statements, we are required to estimate our accrued research and development expenses. This process involves estimating the level of service performed and the associated cost incurred for the service when we have not yet been invoiced or otherwise notified of actual costs. We make estimates of our accrued expenses as of each balance sheet date in the consolidated financial statements based on facts and circumstances known to us at that time. We periodically corroborate the accuracy of these estimates with the service providers and make adjustments, if necessary. Examples of estimated accrued research and development expenses include those related to fees paid to:

Current wording

As part of the process of preparing our consolidated financial statements, we are required to estimate our accrued research and development expenses. This process involves estimating the level of service performed and the associated cost incurred for the service when we have not yet been invoiced or otherwise notified of actual costs. We make estimates of our accrued expenses as of each balance sheet date in the consolidated financial statements based on facts and circumstances known to us at that time. We periodically corroborate the accuracy of these estimates with the service providers and make adjustments, as necessary. Examples of estimated accrued research and development expenses include those related to fees paid to:

Previous wording

We base the expense recorded related to contract research and manufacturing on our estimates of the services received and efforts expended pursuant to quotes and contracts with multiple service providers that conduct services and supply materials. The financial terms of these agreements are subject to negotiation, vary from contract to contract and may result in uneven payment flows. In accruing service fees, we estimate the time period over which services were performed and the level of effort expended in each period. If the actual timing of the performance of services or the level of effort varies from the estimate, we adjust the accrual accordingly. Although we do not expect our estimates to be materially different from amounts actually incurred, our understanding of the status and timing of services performed relative to the actual status and timing of services performed may vary and may result in reporting amounts that are too high or too low in any particular period. While the majority of our service providers invoice us in arrears for services performed, on a pre-determined schedule or when contractual milestones are met, some require advance payments. There may be instances in which payments made to our vendors will exceed the level of services provided and result in a prepayment of the expense. We record these as prepaid expenses on our consolidated balance sheets.

Current wording

We base the expense recorded related to contract research and manufacturing on our estimates of the services received and efforts expended pursuant to quotes and contracts with multiple service providers that conduct services and supply materials. The financial terms of these agreements are subject to negotiation, vary from contract to contract and may result in uneven payment flows. In accruing service fees, we estimate the time period over which services were performed and the level of effort expended in each period. If the actual timing of the performance of services or the level of effort varies from the estimate, we adjust the accrual accordingly. Although we do not expect our estimates to be materially different from amounts actually incurred, our understanding of the status and timing of services performed relative to the actual status and timing of services performed may vary and may result in reporting amounts that are too high or too low in any particular period. There may be instances in which payments made to our vendors will exceed the level of services provided and result in a prepayment of the expense. We record these as prepaid expenses on our consolidated balance sheets.

Previous wording

We account for all stock-based compensation awards granted as stock-based compensation expense at fair valuein accordance with FASB ASC Topic 718, Compensation—Stock Compensation (ASC 718). Our stock-based payments include stock options and grants of common stock restricted for vesting conditions. The measurement date for awards is the date of grant, and stock-based compensation costs are recognized as expense over the requisite service period, which is generally the vesting period, on a straight-line basis. Stock-based compensation expense is classified in the accompanying consolidated statements of operations based on the function to which the related services are provided. Forfeitures are recorded as they occur.

Current wording

We account for all stock-based compensation awards granted as stock-based compensation expense at fair valuein accordance with FASB ASC Topic 718, Compensation—Stock Compensation (ASC 718). Our stock-based payments include stock options, restricted stock units (“RSUs”), and performance stock units (“PSUs”). We estimate the fair value of stock options granted using the Black-Scholes option-pricing model (“Black-Scholes”) for stock option grants to both employees and non-employees. The fair value of the Company’s common stock is used to determine the fair value of RSUs and PSUs. The Company’s stock-based compensation awards are subject to service-based vesting conditions. Compensation expense related to stock option awards and RSUs awards with only service-based vesting is recognized over the requisite service period, which is generally the vesting period, on a straight-line basis. For PSUs, which also contain performance based vesting criteria, we recognize stock-based compensation expense over the requisite service period using the accelerated attribution method once achievement is probable. Stock-based compensation expense is classified in the accompanying consolidated statements of operations in the same manner in which the award recipient’s payroll costs are classified or in which the award recipient’s service payments are classified.

Previous wording

The fair value of each stock option grant is estimated on the date of grant using the Black-Scholes option-pricing model, which requires inputs based on certain subjective assumptions, including the expected share price volatility, the expected term of the option, the risk-free interest rate for a period that approximates the expected term of the option, and our expected dividend yield. Prior to our IPO, there was no public market for our common stock, and consequently, the estimated fair value of our common stock was determined by our board of directors as of the date of each option grant, with input from management, considering third-party valuations of our common stock as well as our board of directors’ assessment of additional objective and subjective factors that it believed were relevant and which may have changed from the date of the most recent third-party valuation through the date of the grant. These third-party valuations were performed in accordance with the guidance outlined in the American Institute of Certified Public Accountants’ Accounting and Valuation Guide, Valuation of Privately-Held-Company Equity Securities Issued as Compensation(Practice Aid). The Practice Aid identifies various available methods for allocating the enterprise value across classes of series of capital stock in determining the fair value of our common stock at each valuation date. Since our IPO, we have determined the fair market value of our common stock using the closing price of our common stock as reported on the Nasdaq Global Market.

Current wording

The fair value of each stock option grant is estimated on the date of grant using the Black-Scholes option-pricing model, which requires inputs based on certain subjective assumptions, including the expected share price volatility, the expected term of the option, the risk-free interest rate for a period that approximates the expected term of the option, and our expected dividend yield. Prior to our IPO, there was no public market for our common stock, and consequently, the estimated fair value of our common stock was determined by our board of directors as of the date of each option grant, with input from management, considering third-party valuations of our common stock as well as our board of directors’ assessment of additional objective and subjective factors that it believed were relevant and which may have changed from the date of the most recent third-party valuation through the date of the grant. These third-party valuations were performed in accordance with the guidance outlined in the American Institute of Certified Public Accountants’ Accounting and Valuation Guide, Valuation of Privately-Held-Company Equity Securities Issued as Compensation(“Practice Aid”). The Practice Aid identifies various available methods for allocating the enterprise value across classes of series of capital stock in determining the fair value of our common stock at each valuation date. Since our IPO, we have determined the fair market value of our common stock using the closing price of our common stock as reported on the Nasdaq Global Market on the date of grant.

Previous wording

Research and development expenses were$99.9 million for the year ended December 31, 2023, compared to$66.6 million for the year ended December 31, 2022. The increase of$33.3 million in research and development expenses was primarily attributable to:

Current wording

Research and development expenses were$125.3 million for the year ended December 31, 2024, compared to$99.9 million for the year ended December 31, 2023. The increase of$25.4 million in research and development expenses was primarily attributable to:

Previous wording

•an increase of$19.6 million in internal costs driven by increased headcount in our research and development function, inclusive of stock-based compensation expense of$6.2 million and$4.2 million for the years ended December 31, 2023 and 2022, respectively, and increased facilities costs to support our expanding operations; and

Current wording

•an increase of 10.5 million in personnel related costs driven by increased headcount in our research and development function, inclusive of stock-based compensation expense of$7.8 million and$6.2 million for the years ended December 31, 2024 and 2023, respectively; and

Previous wording

We expect that our research and development expenses will increase as we continue our current research and development activities, continue clinical trials for ENTR-601-44 and our partnered candidate, VX-670, initiate new research programs, continue our preclinical development of therapeutic candidates, and progress ENTR-601-45, ENTR-601-50, and future product candidates, into clinical trials.

Current wording

We expect that our research and development expenses will increase as we advance ENTR-601-44 and ENTR-601-45 through clinical trials, progress ENTR-601-50 and ENTR-601-51 through preclinical development and into clinical trials, and continue to perform discovery work for future product candidates.

Previous wording

General and administrative expenses for the year ended December 31, 2023 were$32.3 million, compared to$30.6 million for the year ended December 31, 2022. The increase of$1.7 million was primarily attributable to the following:

Current wording

General and administrative expenses for the year ended December 31, 2024 were$38.5 million, compared to$32.3 million for the year ended December 31, 2023. The increase of$6.2 million was primarily attributable to the following:

Previous wording

•a$2.3 million increase in personnel-related costs, primarily as a result of the increase in headcount in our general and administrative function, inclusive of stock-based compensation expense of$6.9 million and $5.7 million for the years ended December 31, 2023 and 2022, respectively;

Current wording

•a$5.9 million increase in personnel-related costs, primarily as a result of the increase in headcount in our general and administrative function, inclusive of stock-based compensation expense of$10.1 million and $6.9 million for the years ended December 31, 2024 and 2023, respectively.

Previous wording

Total interest and other income was $15.2 million for theyear ended December 31, 2023, compared to $2.6 million of interest and other income for theyear ended December 31, 2022. This increase is primarily driven by higher interest rates and larger investments in debt securities.

Current wording

Total interest and other income was $19.5 million for theyear ended December 31, 2024, compared to $15.2 million of interest and other income for theyear ended December 31, 2023. This increase is primarily driven by higher interest rates and larger investments in debt securities.

Previous wording

Since our inception in 2016, we have incurred significant operating losses. As of December 31, 2023 and 2022, we had an accumulated deficit of$195.0 million and$188.3 million, respectively. We expect to continue to generate operating losses and negative operating cash flows for the foreseeable future as we advance our platform and EEV therapeutic candidates. Since our inception, we have raised over $650 million of gross proceeds from sales of stock to leading biotechnology investors and from the Vertex Agreement. As of December 31, 2023, we had cash, cash equivalents and marketable securities of$352.0 million.

Current wording

Since our inception in 2016, we have incurred significant operating losses. As of December 31, 2024 and 2023, we had an accumulated deficit of $129.3 million and $195.0 million, respectively. We expect to generate operating losses and negative operating cash flows for the foreseeable future as we advance our platform and EEV therapeutic candidates. Since our inception, we have raised over $850.0 million of gross proceeds from sales of stock to leading biotechnology investors and from the Vertex Agreement. As of December 31, 2024, we had cash, cash equivalents and marketable securities of $420.0 million.

Previous wording

In September 2023, we entered into a sales agreement (Sales Agreement) with Cowen and Company, LLC (Cowen) under which we may, from time to time, issue and sell shares of our common stock having aggregate sales proceeds of up to $150.0 million, in a series of one or more ATM equity offerings (the 2023 ATM Program). Cowen is not required to sell any specific share amounts but acts as the Company’s sales agent, using commercially reasonable efforts consistent with its normal trading and sales practices. Pursuant to the Sales Agreement, shares will be sold pursuant to our shelf registration statement on Form S-3 (File No. 333-268099) filed with the SEC on November 1, 2022, including the base prospectus contained therein, as declared effective by the SEC on November 7, 2022. The Company’s common stock will be sold at prevailing market prices at the time of the sale, and as a result, prices may vary. As of December 31, 2023, we have not sold any shares of common stock under the ATM program.

Current wording

In September 2023, we entered into a sales agreement (“Sales Agreement”) with Cowen and Company, LLC (“Cowen”) under which we may, from time to time, issue and sell shares of our common stock having aggregate sales proceeds of up to $150.0 million, in a series of one or more ATM equity offerings (the “2023 ATM Program”). Cowen is not required to sell any specific share amounts but acts as the Company’s sales agent, using commercially reasonable efforts consistent with its normal trading and sales practices. Pursuant to the Sales Agreement, shares will be sold pursuant to our shelf registration statement on Form S-3 (File No. 333-268099) filed with the SEC on November 1, 2022, including the base prospectus contained therein, as declared effective by the SEC on November 7, 2022. Our common stock will be sold at prevailing market prices at the time of the sale, and as a result, prices may vary. As of December 31, 2024, we have not sold any shares of common stock under the ATM program.

Previous wording

For the year ended December 31, 2022, net cash used in operating activities was$93.8 million, consisting primarily of our net loss of$94.6 million, a net cash decrease from changes in our operating assets and liabilities of $11.1 million, and adjustments for non-cash items, primarily relating to stock-based compensation expense of$9.9 million, depreciation expense of$1.9 million, and net amortization of premiums and discounts of $0.1 million on marketable securities.

Current wording

For the year ended December 31, 2024, net cash used in operating activities was$41.6 million, and was driven by our net income of$65.6 million, net cash used in changes in our operating assets and liabilities of$118.9 million, adjustments fornon-cash expenses relating to stock-based compensation expense of$17.9 million and depreciation expense of$3.8 million, and adjustments for non-cash income relating to accretion of premiums and discounts on marketable securities of $10.0 million.

Previous wording

For the year ended December 31, 2023, net cash provided by operating activities was$139.8 million, driven by our net loss of$6.7 million, anet cash increase from changes in our operating assets and liabilities of$136.3 million, which was primarily related to the upfront and milestone payment received from Vertex, and adjustments for non-cash items, primarily relating to stock-based compensation expense of$13.1 million, depreciation expense of$2.8 million, and net accretion of premiums and discounts on marketable securities of $5.7 million.

Current wording

For the year ended December 31, 2023, net cash provided by operating activities was$139.8 million, and was driven by our net loss of$6.7 million, net cash provided by changes in our operating assets and liabilities of $136.3 million, adjustments for non-cash expenses relating to stock-based compensation expense of$13.1 million and depreciation expense of$2.8 million, and adjustments for non-cash income related to net amortization of premiums and discounts of $5.7 million on marketable securities.

Previous wording

Net cash used in investing activities was$148.7 million for the year ended December 31, 2022, consisting primarily of $222.0 million in purchases of marketable securities, partially offset by $76.2 million from the maturities of marketable securities, and $2.9 million from purchases of property and equipment.

Current wording

Net cash used in investing activities was$27.8 million for the year ended December 31, 2024, and was driven by$437.7 million in purchases of marketable securities and$3.2 million in purchases of property and equipment, which were partially offset by$413.1 million from the maturities of marketable securities.

Previous wording

Net cash used in investing activities was$138.4 million for the year ended December 31, 2023, consisting primarily of$407.2 million in purchases of marketable securities, partially offset by$274.4 million from the maturities of marketable securities, and$5.6 million in purchases of property and equipment.

Current wording

Net cash used in investing activities was$138.4 million for the year ended December 31, 2023, and was driven by $407.2 million in purchases of marketable securities and$5.6 million from purchases of property and equipment,, which were partially offset by $274.4 million from the maturities of marketable securities.

Previous wording

Net cash provided by financing activities was$0.5 million for the year ended December 31, 2022, consisting of$0.2 million of proceeds from stock option exercises and$0.3 million from the issuance of common stock under our employee stock purchase plan.

Current wording

Net cash provided by financing activitieswas $103.0 million for the year ended December 31, 2024, consisting of$99.6 million in net proceeds from sales of our common stock and pre-funded warrants,$2.8 million proceeds from stock option exercises and$0.6 million from the issuanceof common stock under our 2021 Employee Stock Purchase Plan (the “ESPP”).

Previous wording

Net cash provided by financing activitieswas $21.0 million for the year ended December 31, 2023, consisting of$19.4 million in net proceeds from the issuance of 1,618,613 shares in connection with the Vertex Agreement,$1.2 million proceeds from stock option exercises and$0.4 million from the issuanceof common stock under our employee stock purchase plan.

Current wording

Net cash provided by financing activities was$21.0 million for the year ended December 31, 2023, consisting of$19.4 million in net proceeds from sales of our common stock in connection with the Vertex Agreement, $1.2 million of proceeds from stock option exercises and$0.4 million from the issuance of common stock under the ESPP.

Previous wording

We expect to incur significant expenses and operating losses for the foreseeable future as we advance the preclinical and, if successful, the clinical development of our programs. In addition, we expect to incur additional costs associated with operating as a public company. Our operating expenses and future funding requirements are expected to increase substantially as we continue to advance our portfolio of programs. We believe that our cash, cash equivalents and marketable securities as of December 31, 2023, together with ongoing research support and the anticipated achievement of certain milestones under the Vertex Agreement will be sufficient to extend our cash runway through the second quarter of 2026, supporting the Company's expansion and continued development of EEV therapeutic candidates targeting Duchenne muscular dystrophy and advance EEV-therapeutic candidates in indications beyond neuromuscular disease. We have based this estimate on assumptions that may prove to be wrong, and we could utilize our available capital resources sooner than we expect.

Current wording

We expect to incur significant expenses and operating losses for the foreseeable future as we advance the preclinical and, if successful, the clinical development of our programs. In addition, we expect to incur additional costs associated with operating as a public company. Our operating expenses and future funding requirements are expected to increase substantially as we continue to advance our portfolio of programs. Based on our current operating plans, we believe that our cash, cash equivalents and marketable securities as of December 31, 2024 will be sufficient to fund our operations into the second quarter of 2027. We have based this estimate on assumptions that may prove to be wrong, and we could utilize our available capital resources sooner than we expect.

Previous wording

The Company subleases a portion of the office and laboratory space leased under the IDB Lease to a third-party (subtenant). The term of the sublease commenced in April 2023. The sublease term is 3 years. The initial fixed rental rate is approximately $0.2 million per month and will increase 3% per annum thereafter.

Current wording

The Company subleases a portion of the office and laboratory space leased under the IDB Lease to a third-party. The term of the sublease commenced in April 2023. The sublease term is 3 years. The initial fixed rental rate is approximately $0.2 million per month and will increase 3% per annum thereafter.

Previous wording

We have a noncancellable operating lease of 23,189 square feet of office and laboratory space at 6 Tide Street in Boston, Massachusetts. The term for the lease will end on November 30, 2025. The fixed rental rate is $0.5 million per month for the remainder of the lease term.

Current wording

We have a noncancellable operating lease of 23,189 square feet of office and laboratory space at 6 Tide Street in Boston, Massachusetts. The term for the lease will end on November 30, 2025. The fixed rental rate is $0.4 million per month for the remainder of the lease term.
Rearranged current paragraphs (1)

Current report — wording carried from elsewhere

The Company recorded income tax expense of$0.9 million for the year ended December 31, 2024 and income tax expense of$18.7 million for theyear ended December 31, 2023. The income tax expense recorded for the year ended December 31, 2024 was driven largely 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. The income tax expense recorded for the year ended December 31, 2023 was driven largely by the current tax liability associated with the tax recognition of the upfront payment received pursuant to the Vertex Agreement and the capitalization of research and development expenses under Section 174. For both periods, a significant portion of the taxable income related to the collaboration payments was offset by current year expenses and prior year accumulated losses.
Rearranged previous paragraphs (1)

Previous report — wording carried elsewhere

•CROs in connection with preclinical studies and testing; and