enGene Holdings Inc

Certain statements in this Annual Report on Form 10-K (the “Annual Report”) may constitute “forward-looking statements” within the meaning of U.S. securities laws and “forward-looking information” within the meaning of Canadian securities laws (collectively, “forward-looking statements”). enGene’s forward-looking statements include, but are not limited to, statements regarding enGene’s management teams’ expectations, hopes, beliefs, intentions, goals or strategies regarding the future. In addition, any statements that refer to projections, forecasts or other characterizations of future events or circumstances, including any underlying assumptions, are forward-looking statements. The words “anticipate,” “appear,” “approximate,” “believe,” “continue,” “could,” “estimate,” “expect,” “foresee,” “intends,” “may,” “might,” “plan,” “possible,” “potential,” “predict,” “project,” “seek,” “should,” “would” and similar expressions (or the negative version of such words or expressions) may identify forward-looking statements, but the absence of these words does not mean that a statement is not forward-looking. Forward-looking statements in this Annual Report may include, for example, statements about:

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our financial performance, including financial projections and business metrics and any underlying assumptions thereunder;

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our ability to maintain the listing of the Company’s common shares (“Common Shares”) and warrants to purchase Common Shares (“Warrants”) on The Nasdaq Global Market (“Nasdaq”) or another national securities exchange;

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our success in recruiting and retaining, or changes required in, officers, key personnel or directors;

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our plans and ability to execute product development, manufacturing process development, preclinical and clinical development efforts successfully and on anticipated timelines;

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our ability to design, initiate and successfully complete clinical trials and other studies for detalimogene voraplasmid, or detalimogene, formerly referred to as EG-70, and any other product candidates we develop and our plans and expectations regarding our ongoing or planned clinical trials;

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the impacts and outcomes of our later-stage and pivotal clinical trials and their influence on obtaining the U.S. Food and Drug Administration (the “FDA”) or comparable foreign regulatory approval to market detalimogene or any future product candidates;

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our plans and ability to seek, obtain and maintain marketing approval from the FDA and other regulatory authorities, including the European Medicines Agency (the “EMA”), for detalimogene or any other product candidates we develop;

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our plans and ability to commercialize detalimogene or any other product candidates we develop, if approved by applicable regulatory authorities;

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the degree of market acceptance of detalimogene or any other product candidates we develop, if approved, and the availability of third-party coverage and reimbursement;

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the ability of our external contract manufacturers to support the manufacturing, release testing, stability analysis, clinical labeling and packaging of detalimogene or any other product candidates that we develop;

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our future financial performance and the sufficiency of our cash and cash equivalents to fund our operations;

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our ability to obtain additional funding on a timely basis;

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our ability to effectively manage the transition of executive-level roles to new leaders, and to attract and retain key executives and employees;

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the outcome of any known and unknown litigation and regulatory proceedings, including any legal proceedings that may be instituted against us or any of our directors or officers; and

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our ability to implement and maintain effective internal controls.

All forward-looking statements, including, without limitation, our examination of historical operating trends, are based upon our current expectations and various assumptions. Certain assumptions made in preparing the forward-looking statements include:

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we are able to recruit and retain qualified scientific and management personnel, establish clinical trial sites and patient registration for clinical trials and acquire technologies complementary to, or necessary for, detalimogene or any other programs;

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we are able to enroll, in a timely manner, a sufficient number of patients in each cohort of the Phase 2 LEGEND trial to assess the efficacy and safety of detalimogene including, the pivotal cohort, the cohort with the BCG-naïve patient population, the BCG-exposed patient population and the BCG-unresponsive, papillary-only Ta/T1 disease;

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we are able to file our planned Biologics License Application in mid-2026 with the FDA for approval to market detalimogene in the United States as a monotherapy to treat BCG-unresponsive NMIBC with CIS;

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detalimogene’s product profile can be integrated seamlessly into community urology clinics where the vast majority of NMIBC patients are treated;

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we are able to retain commercial rights to detalimogene in the United States and commercialize detalimogene independently, while selectively partnering outside of the United States;

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we are able to execute the “pipeline-in-a-product” development strategy for detalimogene; and

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we are able to utilize the DDX gene delivery platform to develop effective, new product candidates for the delivery of genetic medicines to mucosal tissues.

You should not place undue reliance on these forward-looking statements which speak only as of the date hereof. The forward-looking statements contained in this Annual Report are based primarily on current expectations and projections about future events and trends that may affect our business, financial condition and operating results. The following uncertainties and factors, among other things (including those described in “Risk Factors” in this Annual Report), could affect future performance and actual results to differ materially and adversely from those expressed in, anticipated or implied by forward-looking statements:

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risks applicable to our business, including the heavy dependence on the success of detalimogene and the extensive regulation of all aspects of our business, competition from other existing or newly developed products and treatments;

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risks associated with the protection of intellectual property, our ability to raise additional capital to fund our product development activity, and our ability to maintain key relationships and to attract and retain talented personnel;

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the possibility that we may be adversely affected by changes in domestic and foreign business, market, financial, political, geopolitical, legal conditions and laws and regulations;

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the risk that any regulatory approvals are not obtained, are delayed or are subject to unanticipated conditions that could adversely affect our business; or

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other risks and uncertainties set forth in the section entitled “Risk Factors” in this Annual Report.

In addition, statements that “we believe” and similar statements reflect beliefs and opinions on the relevant subject. These statements are based on information available to us as of the date of this Annual Report. While we believe that information provides a reasonable basis for these statements, that information may be limited or incomplete. Our statements should not be read to indicate that we have conducted an exhaustive inquiry into, or review of, all relevant information. These statements are inherently uncertain, and investors are cautioned not to unduly rely on these statements.

The forward-looking statements made in this Annual Report relate only to events as of the date on which the statements are made. We undertake no obligation to update any forward-looking statements made in this Annual Report to reflect events or circumstances after the date of this Annual Report or to reflect new information or the occurrence of unanticipated events, except as required by law. We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements.

RISK FACTORS SUMMARY

Our business is subject to a number of risks and uncertainties, including those described in Part I, Item 1A. “Risk Factors” in this Annual Report. The principal risks and uncertainties affecting our business includes, among other the following:

Risks Related to Our Business

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We depend heavily on the success of our lead product candidate, detalimogene voraplasmid, or detalimogene, formerly known as EG-70, which is currently in a clinical trial. Our clinical trial of detalimogene may not be successful. If we are unable to successfully develop, obtain regulatory approval for, and commercialize detalimogene, or experience significant delays in doing so, our business will be materially harmed.

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We expect to make significant investments in our continued research and development of detalimogene and other new product candidates, genetic medicines and services we may develop, which, if not successful, would limit our ability to achieve or sustain profitability in the future.

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The estimates of market sizes and forecasts of market growth for the potential demand of our detalimogene product and any other product candidates we develop are based on a number of assumptions and may prove to be inaccurate. The actual market may be smaller than we believe, which would adversely affect our business and results of operations.

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We identified material weaknesses in our internal control over financial reporting and our management has determined that our current internal control over financial reporting is not effective. If we are unable to remedy these material weaknesses, or if we fail to establish and maintain effective internal controls, we may be unable to produce timely and accurate financial statements, and we may continue to determine that our internal control over financial reporting is not effective, which could adversely impact our investors’ confidence and the price of our Common Shares.

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To date, we have not generated any product revenue, have a history of losses and will need to raise additional capital to fund our operations. If we fail to obtain necessary financing, we will not be able to complete the development and commercialization of detalimogene or our other product candidates.

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We face significant competition from other entities, including biotechnology and pharmaceutical companies, which may result in our competitors discovering, developing or commercializing products before us or more successfully than we do. Our business and results of operations could be adversely affected if we fail to compete effectively.

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We are focusing our research and development efforts on detalimogene, as well as further development of our genetic medicine platform and other product candidates we may develop. As a result, we may forego or delay pursuit of other genetic medicine technologies or other therapeutic product candidates that provide significant advantages over our platform or product candidates, which could materially harm our business and results of operations.

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Detalimogene and our genetic medicine platform are based on proven novel technologies, which makes it difficult to predict the time and cost of development and the probability or timing of subsequently obtaining regulatory approval.

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Development of new therapeutics involves a lengthy and expensive process, with an uncertain outcome. We may incur additional costs, fail to replicate the positive results from our earlier preclinical or clinical studies of our product candidates in later preclinical studies or clinical trials or experience delays in completing or ultimately be unable to complete, the development and commercialization of any product candidates, including but not limited to detalimogene.

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Interim top-line and preliminary data from our clinical trials will change as more patient data become available and are subject to audit and verification procedures that could result in material changes in the final data.

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If we encounter difficulties enrolling patients in clinical trials, our clinical development activities could be delayed or otherwise adversely affected.

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Although we have conducted the Phase 1 portion of the LEGEND clinical study of detalimogene, we have not as an organization completed later-stage or pivotal clinical trials or submitted a BLA (as defined below), and we may be unable to do so for detalimogene or any future product candidates in a timely manner or at all.

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Our use of third parties to manufacture, develop and test our therapeutic product candidates for preclinical studies and clinical trials increases the risk that we will not have sufficient quantities of our product candidates or products, or necessary quantities of such materials on time or at an acceptable cost.

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Detalimogene is complex to manufacture, and the manufacturing process for any other product candidates we develop may be similarly complex or more complex, and we may encounter difficulties in production, particularly with respect to scaling our manufacturing capabilities. If we or any of our third-party manufacturers with whom we contract encounter these types of difficulties, our ability to supply detalimogene or any other product candidates we develop for clinical trials or as products for patients, if approved, could be constrained, delayed or stopped, or we may be unable to maintain a commercially viable cost structure.

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The market opportunities for detalimogene and any other product candidates we develop may be limited to a small group of patients who are ineligible for or have failed prior treatments and our estimates of the prevalence of our target patient populations may be inaccurate.

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We depend on our executive team, and if we do not successfully manage the previously announced transitions of our Chief Executive Officer and other executive officers, or if we lose one or more of our executive officers or key employees or are unable to attract and retain highly skilled employees, such events could harm our business.

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Our research and development initiatives, manufacturing processes and business depend on our ability to attract and retain highly skilled scientists and other specialized individuals. We may not be able to attract or retain such qualified scientists and other specialized individuals in the future due to the competition for qualified personnel among life science and technology businesses.

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Nearly all aspects of our activity and our products and services are subject to extensive regulation by various U.S. federal and state agencies and regulatory bodies in non-U.S. jurisdictions, and compliance with existing or future regulations could result in unanticipated expenses or limit our ability to offer our products and services. Regulatory approval is a lengthy, expensive, and inherently unpredictable process with uncertain outcomes and cost and is subject to the potential for substantial delays. We cannot give any assurance whether or when our product candidates will receive regulatory approval, which is necessary before they can be commercialized.

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We cannot predict whether or when we will obtain regulatory approval to commercialize detalimogene or any other product candidate we may develop in the United States or any other jurisdiction and any such approval may be for a narrower indication than we seek.

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If we are not able to obtain or if there are delays in obtaining required regulatory approvals for detalimogene or any other product candidates that we may develop, our ability to generate revenue will be adversely affected. Even if we eventually gain approval for detalimogene or any other product candidates, we may be unable to commercialize them.

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We may not obtain or maintain regulatory approval of detalimogene or other product candidates we develop in all jurisdictions in which such approval may be required or otherwise desirable or beneficial from a business perspective, and failure to do so may have a material adverse effect on our business and results of operations.

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Our contract manufacturers are subject to significant regulation with respect to the manufacturing of our current and future product candidates. The manufacturing facilities on which we rely may not meet or continue to meet regulatory requirements and/or may have limited capacity.

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Drug marketing, price controls and reimbursement regulations may materially affect our ability to market and receive coverage for our product candidates, if approved, in the European Union, the United Kingdom, Japan and other non-U.S. jurisdictions.

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Global economic uncertainty, changes in geopolitical conditions and weakening product demand caused by political instability, changes in trade agreements and disputes, such as armed conflicts between Russia and Ukraine and in the Middle East, and other macroeconomic factors, could adversely affect our business and results of operations.

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If we are unable to obtain and maintain, enforce and defend patent protection for any product candidates we develop or for our novel genetic medicine platform, or if the scope of the patent protection obtained is not sufficiently broad, our ability to successfully commercialize any product candidates we may develop and our technology may be adversely affected.

Risks Related to our Common Shares and Warrants and to Being a Public Company

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Sales of Common Shares, or the perception of such sales, by us or the Selling Holders in the public market or otherwise could cause the market price for our Common Shares to decline and certain Selling Holders still may receive a significant rate of return.

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Certain existing securityholders acquired their securities in our Company at prices that may be below the current trading price of such securities, and may experience a positive rate of return based on such current trading price. Future investors in our Company may not experience a similar rate of return.

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There is no assurance that Warrants will be and/or remain “in the money” prior to their expiration or that the holders of Warrants will elect to exercise any or all of their Warrants for cash; the Warrants may expire worthless.

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We will continue to incur increased costs as a result of operating as a public company, and the requirements for public companies may strain resources and divert management’s attention.

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We may be unable to satisfy Nasdaq’s continued listing requirements in the future, which could limit investors’ ability to effect transactions in our securities and subject us to additional trading restrictions.

Part I