What changed in this filing

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Item 1A. Risk Factors

2025-07-29 compared with 2025-05-09 · 73 added, 52 removed, 1070 unchanged (10% of the section changed)

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A failure of AMT-130 in clinical development, including inability to demonstrate sufficient safety or efficacy, or challenges associated with its regulatory approval, manufacturing or commercialization could adversely affect our business.

● We will need to raise additional funding in order to advance the development of our product candidates and support the commercial launch of AMT-130, which may not be available on acceptable terms, or at all.

Failure to obtain capital when needed may force us to delay, limit or terminate our product development efforts or other operations, which could have a material adverse effect on our business, financial condition, results of operations and cash flows.

● We have encountered and may encounter future delays in and impediments to the progress of our clinical trials or fail to demonstrate the safety and efficacy of our product candidates.

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● The risks associated with the marketing approval process are heightened by the status of our products as gene therapies.

● We may leverage certain specialized regulatory pathways and designations, such as the FDA’s accelerated approval pathway and RMAT designation, to develop our product candidates or to seek licensure.

● We may leverage certain specialized regulatory pathways and designations, such as the FDA’s accelerated approval pathway, RMAT designation and Breakthrough Therapy designation, to develop our product candidates or to seek licensure.

Even if one or more of our product candidates receives such a designation or is permitted to pursue such a pathway, we may be unable to obtain and maintain the benefits associated with such designations and pathways.

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● The market price of our ordinary shares has been and may in the future be volatile and fluctuate substantially.

● Our future success depends on our ability to retain key executives, technical staff, and other employees and to attract, retain and motivate qualified personnel.

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In July 2024, we announced updated interim data from our ongoing Phase I/II clinical trials of AMT-130.

This interim data follows notification from FDA in May 2024 that the agency granted RMAT designation for AMT-130 based on AMT-130’s potential to address the major unmet medical need among patients with Huntington’s disease.

In addition, in December 2024, following our initial Type B meeting, we announced that we had reached agreement with FDA on key elements of an Accelerated Approval pathway for AMT-130, including that data from the ongoing Phase I/II studies of AMT-130, compared to a natural history external control, may serve as the primary basis for a BLA submission under FDA’s Accelerated Approval pathway.

FDA also agreed that cUHDRS may be used as an intermediate clinical endpoint and that reductions in NfL measured in CSF may serve as supportive evidence of therapeutic benefit in the application for accelerated approval.

We have initiated BLA-readiness activities and have had additional interactions with the FDA in March and April 2025 to discuss the pivotal statistical analysis plan and CMC requirements for a BLA submission.

This interim data follows notification from the FDA in June 2024 that the agency granted RMAT designation for AMT-130 based on AMT-130’s potential to address the major unmet medical need among patients with Huntington’s disease.

In addition, in December 2024, following our initial Type B meeting, we announced that we had reached agreement with the FDA on key elements of an accelerated approval pathway for AMT-130, including that data from the ongoing Phase I/II studies of AMT-130, compared to a natural history external control, may serve as the primary basis for a BLA submission under the FDA’s accelerated approval pathway.

The FDA also agreed that cUHDRS may be used as an intermediate clinical endpoint and that reductions in NfL measured in CSF may serve as supportive evidence of therapeutic benefit in the application for accelerated approval.

We have initiated BLA-readiness activities and have had additional interactions with the FDA in March and April 2025 to discuss the pivotal SAP and CMC requirements for a BLA submission.

In June 2025, we announced additional alignment with the FDA toward a planned BLA submission for AMT-130.

In addition, in April 2025, we announced that the FDA has granted Breakthrough Therapy designation to AMT-130.

This designation is in addition to the FDA’s previously granted RMAT, Orphan Drug and Fast Track designations for the AMT-130 program.

Breakthrough Therapy designation is intended to expedite the development and review of investigational therapeutic candidates that are intended to treat a serious condition and for which preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s) by ensuring that drug is eligible for all Fast Track designation features, intensive guidance on an efficient drug development program, and FDA commitment involving senior managers.

There are numerous factors that could impede or otherwise negatively impact our further development of AMT-130, including, but not limited to, potential patient safety issues;

our failure to demonstrate sufficient clinical efficacy or durability of response data to warrant further development or accelerated approval by FDA, EMA or any other regulatory authority;

our ability to achieve alignment with FDA and other regulatory authorities on the pivotal statistical analysis plan and CMC requirements to support registration, the timing of such regulatory alignment and other factors impacting our interactions with FDA which may be outside of our control;

the results from future interim data readouts from our Phase I/II trial, including the three-year follow-up data from treated patients and safety and tolerability data from the third cohort;

our failure to demonstrate sufficient clinical efficacy or durability of response data to warrant further development or accelerated approval by the FDA, EMA or any other regulatory authority;

our ability to achieve alignment regarding an accelerated approval pathway for AMT-130 with the FDA and the timing of such regulatory alignment and other factors impacting our interactions with the FDA which may be outside of our control;

our current beliefs regarding the further development of AMT-130 are based on our interpretation of communications and interactions with the FDA to date, and our efforts to address such communications and interactions, including regulatory authority minutes, may be incorrect;

the results from future interim data readouts from our Phase I/II trial, including the three-year follow-up data from treated patients;

any requirement for a Phase III confirmatory study;

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Certain of these risk factors are heightened in the context of drug development for rare diseases like Huntington’s disease and novel investigational products like gene therapies in which non-traditional study designs are utilized to demonstrate efficacy and safety, including open-label studies, single arm studies, studies utilizing active comparators or natural history data, biomarkers or other forms of surrogate endpoints, which may be utilized due to the challenges inherent in designing and conducting clinical trials for severe diseases that progress slowly and that affect small patient populations.

Notwithstanding alignment with FDA on key elements of the accelerated approval pathway, we cannot be certain that AMT-130, or any of our product candidates, will be successful in clinical trials or receive regulatory approval.

If we were required to, or if we chose to, discontinue development of AMT-130 or any other current or future product candidates, or if any of them were to fail to receive regulatory approval or achieve sufficient market acceptance, we could be prevented from or significantly delayed in achieving profitability and our business would be adversely affected.

Notwithstanding alignment with the FDA on the key elements of the accelerated approval pathway for AMT-130, the FDA has broad discretion with regard to licensure through the accelerated approval program and even if we believe that an accelerated approval program is appropriate for AMT-130, we cannot be certain that the FDA will not require additional studies and trials beyond those that we currently contemplate.

Furthermore, even if the FDA reviews a BLA seeking accelerated approval, there can be no assurance that licensure will be granted on a timely basis, or at all.

The FDA may disagree that the design of, or results from, our studies and SAP support accelerated approval.

Additionally, the FDA could require us to conduct further studies or trials prior to granting licensure of any type, including by determining that licensure through the accelerated approval program is not appropriate and that our clinical trials and SAP for AMT-130 may be used to support licensure through the conventional pathway.

We might not be able to fulfill the FDA’s requirements in a timely manner, which would cause delays, or licensure might not be granted because our submission is deemed incomplete by the FDA.

Furthermore, the feedback or requests we receive from the FDA, or other non-U.S.

regulatory authority, may be difficult to implement or not implementable at all.

There also can be no assurance that after subsequent FDA feedback we will continue to pursue licensure through the accelerated approval program.

A failure to obtain licensure for AMT-130 could result in a longer time period to obtain licensure of our products, could increase the cost of our products’ development, could delay our ability to launch and commercialize AMT-130 in the United States and could significantly harm our financial position and competitive position in the marketplace.

We cannot be certain that AMT-130, or any of our product candidates, will be successful in clinical trials or receive regulatory approval.

If we were required to, or if we chose to, discontinue development of AMT-130 or any other current or future product candidate, or if any of them were to fail to receive regulatory approval or achieve sufficient market acceptance, we could be prevented from or significantly delayed in achieving profitability and our business would be adversely affected.

We have encountered and may encounter future delays in and impediments to the progress of our clinical trials or fail to demonstrate the safety and efficacy of our product candidates.

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and Europe for AMT-130, our investigational gene therapy for the treatment of Huntington’s disease.

In June 2024, we announced that the FDA granted Regenerative Medicine Advanced Therapy (“RMAT”) designation for AMT-130 based on the potential of AMT-130 to address the major unmet medical need among patients with Huntington’s disease.

Following our initial Type B meeting with the FDA, we announced in December 2024 that we had reached agreement with FDA on key elements of an accelerated approval pathway for AMT-130 and have initiated BLA readiness activities based on this regulatory alignment.

In June 2024, we announced that the FDA granted RMAT designation for AMT-130 based on the potential of AMT-130 to address the major unmet medical need among patients with Huntington’s disease.

Following our initial Type B meeting with the FDA, we announced in December 2024 that we had reached agreement with the FDA on key elements of an accelerated approval pathway for AMT-130 and have initiated BLA readiness activities based on this regulatory alignment.

In addition, in April 2025, we announced that the FDA had granted Breakthrough Therapy designation to AMT-130.

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● delays in receiving regulatory authorization to conduct our clinical trials or a regulatory authority decision that the clinical trial should not proceed;

● failures or delays in obtaining or failure to obtain required IRB and IBC approval at each clinical trial site;

● failures or delays in obtaining or failure to obtain required Institutional Review Board (“IRB”) and Institutional Biosafety Committee (“IBC”) approval at each clinical trial site;

● requirements of regulatory authorities, IRBs, or IBCs to modify a study in such a way that it makes the study impracticable to conduct;

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● disagreements with regulatory authorities regarding our study design, including endpoints, our chosen indication, our chosen bases for comparison as it relates to measurements of clinical efficacy, our interpretation and statistical analyses of data collected from preclinical studies and clinical trials;

● recommendations from DSMBs to discontinue, pause, or modify the trial;

● recommendations from Data and Safety Monitoring Boards (“DSMBs”) to discontinue, pause, or modify the trial;

● imposition of a clinical hold by regulatory agencies after an inspection of our clinical trial operations or trial sites;

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Accordingly, the results from our open-label trials, including early indications of potential efficacy, may not be predictive of future clinical trial results.

Early evidence of slowing of disease progression in our AMT-130 clinical trial may not be predictive of continued evidence of potential efficacy as we continue to collect follow-up data from patients enrolled in the trial.

Early evidence of slowing disease progression in our AMT-130 clinical trial may not be predictive of continued evidence of potential efficacy as we continue to collect follow-up data from patients enrolled in the trial.

Interim or preliminary results from our clinical trials may change as more data become available, as such data are subject to regulatory audit and verification procedures, and regulatory review, which could result in material changes in the final results and conclusions.

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Accordingly, third parties, including regulatory agencies, may not accept or agree with our assumptions, estimates, calculations, conclusions, or analyses or may interpret or weigh the importance of data differently, which could negatively impact the value of the particular program, its prospects for approval and our business.

In December 2024, following our initial Type B meeting, we announced that we had reached agreement with FDA on key elements of an accelerated approval pathway for AMT-130, including that data from the ongoing Phase I/II studies of AMT-130, compared to a natural history external control, may serve as the primary basis for a BLA submission under FDA’s Accelerated Approval pathway.

Notwithstanding alignment with the agency on these elements, and notwithstanding our recent receipt of Breakthrough Designation for the AMT-130 program, we may fail to continue to demonstrate clinical efficacy or durability of response data to warrant further development or accelerated approval by FDA, EMA or any other regulatory authority.

In December 2024, following our initial Type B meeting, we announced that we had reached agreement with the FDA on key elements of an accelerated approval pathway for AMT-130, including that data from the ongoing Phase I/II studies of AMT-130, compared to a natural history external control, may serve as the primary basis for a BLA submission under the FDA’s accelerated approval pathway.

In addition, the information we choose to publicly disclose regarding a particular study or clinical trial may be top-line results based on what is typically extensive information, and others may not agree with what we determine is the material or otherwise appropriate information to include in our public disclosures.

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We face worldwide competition from larger pharmaceutical companies, specialty pharmaceutical companies and biotechnology firms, universities and other research institutions and government agencies that are developing and commercializing pharmaceutical products.

Our key competitors focused on developing therapies in various indications, include among others, PTC Therapeutics, Roche, Wave Life Sciences, Alnylum Pharmaceuticals, Regeneron and Skyhawk Therapeutics (for Huntington’s disease), Neurona and Combigene (for TLE), Biogen, Ionis, Neurimmune, Regeneron, Alnylum Pharmaceuticals and Voyager Therapeutics (for ALS) and Amicus Therapeutics, Sanofi, Takeda, Chiesi, Idorsia, Sangamo Therapeutics, 4D Molecular Therapeutics, Skyline Pharmaceuticals and CANbridge (for Fabry disease).

Our key competitors focused on developing therapies in various indications, include among others, Novartis (through an exclusive license from PTC Therapeutics), Roche, Wave Life Sciences, Alnylum Pharmaceuticals, Regeneron and Skyhawk Therapeutics (for Huntington’s disease), Neurona and Combigene (for TLE), Biogen, Ionis, Neurimmune, Regeneron, Alnylum Pharmaceuticals and Voyager Therapeutics (for ALS) and Amicus Therapeutics, Sanofi, Takeda, Chiesi, Idorsia, Sangamo Therapeutics, 4D Molecular Therapeutics, Skyline Pharmaceuticals and CANbridge (for Fabry disease).

Our commercial opportunity and/or the receipt of royalties from the sale of any approved products (should we chose to commercialize our products with a commercial partner) could be reduced or eliminated if our competitors develop and commercialize products that are safer, more effective, have fewer or less severe side effects, are more convenient or are less expensive than the products that we develop.

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Further, any marketing approval we ultimately obtain may be for only limited indications or be subject to stringent labeling or other restrictions or post-approval commitments that render the approved product not commercially viable.

Disruptions at the FDA, and other government agencies, from funding cuts, personnel losses, leadership changes, regulatory reform, government shutdowns and other developments could hinder our ability to obtain further guidance from the FDA regarding our clinical development programs and secure approval of our product candidates in a timely manner, which could adversely affect our business.

The FDA and comparable regulatory agencies in foreign jurisdictions play an important role in the development of our product candidates by providing guidance on our clinical development programs and reviewing our regulatory submissions.

If these oversight and review activities are disrupted, then correspondingly our ability to develop and secure timely approval of our product candidates could be impacted in a negative manner.

For example, the recent loss of FDA leadership and personnel, including the administration’s recent reduction in force and budget cuts, and new leadership at the U.S.

Department of Health and Human Services, FDA and the Center for Drug Evaluation and Research could lead to disruptions and delays in FDA guidance and review and approval of our product candidates, including AMT-130.

There is also substantial uncertainty as to how regulatory reform measures being implemented by the current U.S.

presidential administration across the government will impact the FDA and other federal agencies with jurisdiction over our activities.

For example, since taking office, the U.S.

President has issued a number of executive orders that could have a significant impact on the manner in which the FDA conducts its operations and engages in regulatory and oversight activities.

If these or other orders or executive actions impose constraints on the FDA’s ability to engage in oversight and implementation activities in the normal course, our business may be adversely affected.

The risks associated with the marketing approval process are heightened by the status of our products as gene therapies.

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In the U.S., there have been a number of changes relating to gene therapy development.

By example, FDA issued a number of guidance documents, and continues to issue guidance documents, on human gene therapy development, one of which was specific to human gene therapy for hemophilia, one that was specific to neurodegenerative diseases, and another of which was specific to rare diseases.

By example, the FDA issued a number of guidance documents, and continues to issue guidance documents, on human gene therapy development, one of which was specific to human gene therapy for hemophilia, one that was specific to neurodegenerative diseases, and another of which was specific to rare diseases.

Under proposed EU legislation, there is also a suggested amendment in relation to advanced therapy medicinal products to the effect that hospital pharmacies would be afforded greater flexibility to prepare product for dispensing on the basis of the estimated prescriptions within that hospital for the following 7 days rather than, as at present, in response to individual prescriptions.

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Delay or failure to obtain, or unexpected costs in obtaining, the regulatory approval necessary to bring a potential product to market could decrease our ability to generate sufficient product revenues to maintain our business.

We may leverage certain specialized regulatory pathways and designations, such as the FDA’s accelerated approval pathway and RMAT designation, to develop our product candidates or to seek licensure.

We may leverage certain specialized regulatory pathways and designations, such as the FDA’s accelerated approval pathway, RMAT designation and Breakthrough Therapy designation, to develop our product candidates or to seek licensure.

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Biologics studied for their safety and effectiveness in treating serious or life-threatening illnesses and that provide meaningful therapeutic benefit over existing treatments may also receive accelerated approval by the FDA, meaning the agency may approve the product candidate based upon a surrogate endpoint that is reasonably likely to predict clinical benefit, or on a clinical endpoint that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit.

As part of our alignment with FDA in December 2024 on the accelerated approval pathway for AMT-130, the agency agreed that cUHDRS may be used as an intermediate clinical endpoint and that reductions in NfL measured in CSF may serve as supportive evidence of therapeutic benefit in the application for accelerated approval.

There is no guarantee that we would be able to obtain accelerated approval as FDA may disagree with our interim endpoint or may find that such endpoint is not met following subsequent clinical data.

As part of our alignment with the FDA in December 2024 on the accelerated approval pathway for AMT-130, the agency agreed that cUHDRS may be used as an intermediate clinical endpoint and that reductions in NfL measured in CSF may serve as supportive evidence of therapeutic benefit in the application for accelerated approval.

There is no guarantee that we would be able to obtain accelerated approval as the FDA may disagree with our interim endpoint or may find that such endpoint is not met following subsequent clinical data.

These designations and accelerated approval pathways may not lead to a faster development or regulatory review or approval process and may not increase the likelihood that our product candidates will receive marketing approval.

Even though we have aligned with the FDA on elements of the accelerated approval pathway for AMT-130, we may not ultimately be successful in obtaining marketing approval for AMT-130, we may be unsuccessful in meeting post-marketing compliance requirements, or fail to conduct required post-approval studies, or to confirm a clinical benefit during post-marketing studies, which could result in the FDA withdrawing our product from the market.

In recent years, the accelerated approval pathway has come under significant FDA and public scrutiny and it is unclear how the incoming Trump Administration in the U.S.

In recent years, the accelerated approval pathway has come under significant FDA and public scrutiny and it is unclear how the current presidential administration in the U.S.

will address regulations related to accelerated approval pathways, if at all.

Accordingly, it is uncertain whether the FDA may be more conservative in granting accelerated approval or, if granted, more apt to withdraw approval if clinical benefit is not confirmed.

There is no guarantee that regulatory interactions with FDA or comparable foreign authorities will result in our ability to avail ourselves of any specialized approval pathways for our product candidates.

There is no guarantee that regulatory interactions with the FDA or comparable foreign authorities will result in our ability to avail ourselves of any specialized approval pathways for our product candidates.

Our failure to obtain or maintain orphan product exclusivity for any of our product candidates for which we seek this status could limit our commercial opportunity, and if our competitors are able to obtain orphan product exclusivity before we do, we may not be able to obtain approval for our competing products for a significant period.

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By example, in the U.S., whether two gene therapies are considered to be the same for the purpose of determining clinical superiority was updated via a final guidance document specific to gene therapies, and depends on a number of factors, including the expressed transgene, the vector, and other product or product candidate features.

Depending on the products, whether two products are ultimately considered to be the same may be determined by FDA on a case-by-case basis, making it difficult to make predictions regarding when the FDA might be able to make an approval of a product effective and whether periods of exclusivity will effectively block competitors seeking to market products that are the same or similar to ours for the same intended use.

Depending on the products, whether two products are ultimately considered to be the same may be determined by the FDA on a case-by-case basis, making it difficult to make predictions regarding when the FDA might be able to make an approval of a product effective and whether periods of exclusivity will effectively block competitors seeking to market products that are the same or similar to ours for the same intended use.

Accordingly, whether any of our gene therapies will be deemed to be the same as another product or product candidate is uncertain.

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Moreover, if a company obtains FDA approval for a product via the accelerated approval pathway, the company would be required to conduct a post-marketing confirmatory trial to verify and describe the clinical benefit in support of full approval.

FDA can, and frequently does, require that this confirmatory trial be commenced prior to FDA granting a product accelerated approval.

If FDA requires that a confirmatory study be underway prior to BLA approval, this could delay any planned BLA submissions and FDA marketing approvals.

The FDA can, and frequently does, require that this confirmatory trial be commenced prior to the FDA granting a product accelerated approval.

If the FDA requires that a confirmatory study be underway prior to BLA approval, this could delay any planned BLA submissions and FDA marketing approvals.

Moreover, an unsuccessful post-marketing study or failure to complete such a study could result in the expedited withdrawal of the FDA’s marketing approval for a product using a statutorily defined streamlined process.

Changes to some of the conditions established in an approved application, including changes in labeling, indications, manufacturing processes or facilities, may require a submission to and approval by the FDA or the EMA, as applicable, before the change can be implemented.

A New Drug Application (“NDA”)/BLA or MAA supplement for a new indication typically requires clinical data similar to that in the original application.

A New Drug Application (“NDA”)/BLA or Marketing Authorization Application (“MAA”) supplement for a new indication typically requires clinical data similar to that in the original application.

The applicable regulatory authorities would review such supplement using similar procedures and actions as in reviewing NDAs/BLAs and MAAs.

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Regulatory authorities may withdraw product approvals or request product recalls, as well as impose other enforcement actions, if a company fails to comply with regulatory standards, if it encounters problems following initial marketing, or if previously unrecognized problems are subsequently discovered.

In addition, the manufacture, testing, packaging, labeling, and distribution of products after approval will need to continue to conform to cGMPs.

In addition, the manufacture, testing, packaging, labeling, and distribution of products after approval will need to continue to conform to current Good Manufacturing Practices (“cGMPs”).

Drug and biological product manufacturers, including us, and certain of their subcontractors are subject to periodic unannounced inspections by the FDA or the EMA for compliance with cGMPs.

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The Lexington Transaction may not yield the benefits that we expect and may result in additional risks to our business, including those related to Genezen’s ability to manufacture HEMGENIX in accordance with regulatory requirements and to meet CSL Behring’s supply requirements for commercial product.

In connection with the closing of the Lexington Transaction in July 2024, we and Genezen entered into certain additional agreements, including a commercial supply agreement pursuant to which Genezen will manufacture and supply our requirements of HEMGENIX® pursuant to our manufacturing and supply obligations to CSL Behring, and development and other manufacturing services agreement pursuant to which Genezen will manufacture, supply and provide certain development services to support the requirements of our investigational gene therapy programs and for other discretionary services related to the manufacture of HEMGEMIX®, along with other customary agreements.

As a component of our broader efforts to focus our business and reduce operating expenses, the Lexington Transaction is expected to reduce our cash burn as a result of a reduction in facility and personnel-related costs, among others.

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Following the Lexington Transaction, Genezen is responsible for the manufacturing and supply of HEMGENIX® at the Lexington Facility, though we remain contractually obligated to CSL Behring consistent with the terms of our development and commercial supply agreement with CSL Behring.

While uniQure has priority and preferential status with Genezen, Genezen may not have sufficient capacity to support our other development programs or those of its other customers, which may negatively impact our business and ability to advance development goals unrelated to HEMGENIX® and our obligations to CSL Behring.

While we have priority and preferential status with Genezen, Genezen may not have sufficient capacity to support our other development programs or those of its other customers, which may negatively impact our business and ability to advance development goals unrelated to HEMGENIX® and our obligations to CSL Behring.

The manufacturing of HEMGENIX® pursuant to our obligations under the CSL Behring Agreement is expensive and requires the dedication of significant resources, notwithstanding the Lexington Transaction and our subcontracting to Genezen.

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pertaining to licensed rights of etranacogene dezaparvovec was assumed by CSL Behring in October 2023.

These oppositions and future patent oppositions may result in loss of scope of some claims or the entire patent and, with respect to our rights under the CSL Agreement, could affect CSL Behring’s successful commercialization of HEMGENIX® and, in turn, could negatively impact our financial position.

These oppositions and future patent oppositions may result in loss of scope of some claims or the entire patent and, with respect to our rights under the CSL Behring Agreement, could affect CSL Behring’s successful commercialization of HEMGENIX® and, in turn, could negatively impact our financial position.

Additionally, our competitors may be able to circumvent our owned or licensed patents by developing similar or alternative technologies or products in a non-infringing manner.

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We had net losses in the years ended December 31, 2024 and 2023, have incurred significant losses in previous years and expect to incur losses in the future, and may never achieve or maintain profitability.

We had a net loss of $43.6 million in the three months ended March 31, 2025, and a net loss of $239.6 million in the year ended December 31, 2024.

We had a net loss of $81.4 million in the six months ended June 30, 2025, and a net loss of $239.6 million in the year ended December 31, 2024.

Other than a gain in the year ended December 31, 2021, which was primarily attributable to one-time license revenue from CSL Behring, we have incurred significant losses throughout our operating history.

As of March 31, 2025, we had an accumulated deficit of $1,173.6 million.

As of June 30, 2025, we had an accumulated deficit of $1,211.3 million.

We have financed our operations to date primarily through the sale of equity securities and convertible debt, venture loans, upfront payments from our collaboration partners and, to a lesser extent, subsidies and grants from governmental agencies and fees for services.

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We expect to incur significant expenses in connection with our ongoing activities and we will need to obtain substantial additional funding to support the development of our product pipeline and continuing operations.

In January 2025, we entered into an underwriting agreement in connection with the issuance and sale of 4,411,764 or our ordinary shares at a public offering price of $17.00 per share, less underwriting discounts and commissions, pursuant to a shelf registration statement on Form S-3 and accompanying prospectus (Registration No.

In January 2025, we entered into an underwriting agreement in connection with the issuance and sale of 4,411,764 of our ordinary shares at a public offering price of $17.00 per share, less underwriting discounts and commissions, pursuant to a shelf registration statement on Form S-3 and accompanying prospectus (Registration No.

333-284168), which became effective upon filing on January 7, 2025, and a prospectus supplement thereunder.

We received net proceeds of approximately $70.1 million from the January 2025 equity offering, after deducting underwriting discounts and commissions and other offering expenses payable by us.

We received an additional $10.6 million in net proceeds in February 2025 from the underwriters’ exercise of their option to purchase additional ordinary shares at the public offering price.

Based on our current operating plan, research and development plans and our timing expectations related to the progress of our programs, we believe that our existing cash and cash equivalents and investment securities will be sufficient to fund our operations through the second half of 2027.

We received an additional $10.4 million in net proceeds after related offering expenses in February 2025 from the underwriters’ exercise of their option to purchase additional ordinary shares at the public offering price.

We have based our current estimates of our financing requirements on assumptions that may prove to be wrong, and we could use our capital resources sooner than we expect.

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Our existing and any future indebtedness could adversely affect our ability to operate our business.

As of March 31, 2025, we had $50.0 million of outstanding principal of borrowings under the 2024 Amended Facility.

As of June 30, 2025, we had $50.0 million of outstanding principal of borrowings under the 2024 Amended Facility.

In July 2024, in connection with the closing of the Lexington Transaction, we repaid $50.0 million of the principal outstanding.

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Such actions could also adversely restrict our business and operations.

There could also be changes in FDA’s approval standards that could impact our ability to obtain BLA approval and market our product candidates within the currently anticipated timeframes or otherwise impact the competitive market for our product candidates.

There could also be changes in the FDA’s approval standards that could impact our ability to obtain BLA approval and market our product candidates within the currently anticipated timeframes or otherwise impact the competitive market for our product candidates.

Such changes may necessitate the conduct of additional development work, including preclinical and clinical trials, and manufacturing development.

By example, for products intended for rare and serious diseases with unmet medical needs, FDA is authorized to exercise regulatory flexibility when making a medical risk-benefit judgment.

It is possible that whether and how FDA exercises any such regulatory flexibility, including with respect to specialized pathways, such as accelerated approval, may change, which could impact our ability to obtain approval for AMT-130 or any of our product candidates.

By example, for products intended for rare and serious diseases with unmet medical needs, the FDA is authorized to exercise regulatory flexibility when making a medical risk-benefit judgment.

It is possible that whether and how the FDA exercises any such regulatory flexibility, including with respect to specialized pathways, such as accelerated approval, may change, which could impact our ability to obtain approval for AMT-130 or any of our product candidates.

Further, legal and regulatory changes may impact how we may market and sell our products in the future, if they are approved, as well as how they are reimbursed.

Moreover, there could be changes in the federal workforce and agency policies that may result in regulatory delays, including with respect to FDA’s review of marketing applications and other submissions, and that may impact the ability to communicate with and obtain guidance from the agencies.

Moreover, there could be changes in the federal workforce and agency policies that may result in regulatory delays, including with respect to the FDA’s review of marketing applications and other submissions, and that may impact the ability to communicate with and obtain guidance from the agencies.

At this time, it is too early to predict the exact nature of any changes that may take place or whether and how they may impact our business and results of operations.

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Our ordinary share price has been and may in the future be volatile.

From the start of trading of our ordinary shares on the Nasdaq Global Select Market on February 4, 2014 through May 6, 2025 the sale price of our ordinary shares ranged from a high of $82.49 to a low of $3.73.

The closing price on May 6, 2025 was $11.48 per ordinary share.

From the start of trading of our ordinary shares on the Nasdaq Global Select Market on February 4, 2014 through July 24, 2025 the sale price of our ordinary shares ranged from a high of $82.49 to a low of $3.73.

The closing price on July 24, 2025 was $15.21 per ordinary share.

In recent years, the stock market in general and the market for shares of biotechnology and biopharmaceutical companies in particular have experienced significant price and volume fluctuations that have often been unrelated or disproportionate to changes in the operating performance of the companies whose stock is experiencing those price and volume fluctuations.

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The loss of the services of any member of our senior management or the inability to hire or retain experienced management personnel could adversely affect our ability to execute our business plan and harm our operating results.

We are highly dependent on hiring, training, retaining, and motivating key personnel to lead our research and development, clinical operations, and manufacturing efforts.

We are highly dependent on hiring, training, retaining, and motivating key personnel to lead our research and development, clinical operations, commercialization and manufacturing efforts.

Although we have entered into employment agreements with our key personnel, each of them may terminate their employment subject to the notice provisions in such agreements.

We do not maintain key person insurance for any of our senior management or employees.

The loss of the services of our key employees could impede the achievement of our research and development objectives and seriously harm our ability to successfully implement our business strategy.

The loss of the services of our key employees could impede the achievement of our research and development and commercialization objectives and seriously harm our ability to successfully implement our business strategy.

Furthermore, replacing senior management and key employees may be difficult and may take an extended period because of the limited number of individuals in our industry with the breadth and depth of skills and experience required to successfully develop gene therapy products.

3 unchanged sentences

We may be adversely affected by unstable market and economic conditions and potential macroeconomic effects, such as inflation, new or increased tariffs and higher interest rates, which may negatively impact our business, financial condition and share price.

Macroeconomic conditions beyond our control such as economic instability, changes in tax laws and regulations, including based on the recent U.S.

presidential election, trade restrictions, additional tariffs, export controls, inflation, high interest rates, volatile energy costs, geopolitical issues, armed hostilities, such as the ongoing conflicts between Russia and Ukraine and in the Middle East, unstable global credit markets and financial conditions could lead to periods of significant economic instability, diminished liquidity and credit availability, diminished expectations for the global economy and expectations of slower global economic growth going forward.

Macroeconomic conditions beyond our control such as economic instability, changes in tax laws and regulations, including those implemented by the current U.S.

presidential administration, trade restrictions, additional tariffs, export controls, inflation, high interest rates, volatile energy costs, geopolitical issues, armed hostilities, such as the ongoing conflicts between Russia and Ukraine and in the Middle East, unstable global credit markets and financial conditions could lead to periods of significant economic instability, diminished liquidity and credit availability, diminished expectations for the global economy and expectations of slower global economic growth going forward.

Our business and operations may be adversely affected by such instability, including any such inflationary fluctuations, economic downturns, volatile business environments and continued unstable or unpredictable economic and market conditions.

57 unchanged sentences

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-Q

Item 1A. Risk Factors