10q10k10q10k.net

What changed in uniQure N.V.'s 10-K — 2023 vs 2024

vs

Paragraph-level year-over-year comparison of uniQure N.V.'s 2023 and 2024 10-K annual filings, covering the Business, Risk Factors, Legal Proceedings, Cybersecurity, MD&A and Market Risk sections. Every new, removed and edited paragraph is highlighted side-by-side so you can see exactly what management changed in the 2024 report.

+579 added−529 removedSource: 10-K (2025-02-27) vs 10-K (2024-02-28)

Top changes in uniQure N.V.'s 2024 10-K

579 paragraphs added · 529 removed · 395 edited across 2 sections

Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

262 edited+111 added−57 removed219 unchanged
Biggest changeThe success of our product candidates will depend on many factors, including: ● successful completion of preclinical studies and clinical trials, and other work required by regulators; ● receipt and maintenance of marketing approvals from applicable regulatory authorities; ● obtaining and maintaining patent and trade secret protection and non-patent, exclusivities for our product candidates; ● maintaining regulatory approvals using our manufacturing facility in Lexington, Massachusetts; ● launch and commercialization of our products, if approved, whether alone or in collaboration with others; ● identifying and engaging effective distributors or resellers on acceptable terms in jurisdictions where we plan to utilize third parties for the marketing and sales of our product candidates; ● acceptance of our products, if approved, by patients, the medical community, and third-party payers; ● effectively competing with existing therapies and gene therapies based on safety and efficacy profiles; 57 ​ Table of Contents ● the strength of our marketing and distribution; ● the achievement optimal pricing based on durability of expression, safety, and efficacy; ● the ultimate content of the regulatory authority approved label, including the approved clinical indications, and any limitations or warnings; ● any distribution or use restrictions imposed by regulatory authorities; ● the interaction of our products with any other medicines that patients may be taking or the restriction on the use of our products with other medicines; ● the standard of care at the time of product approval; ● the relative convenience and ease of administration of our products; ● obtaining healthcare coverage and adequate reimbursement of our products; ● any price concessions, rebates, or discounts we may need to provide; ● complying with any applicable post-approval commitments and requirements, and maintaining a continued acceptable overall safety profile; and ● obtaining adequate reimbursement for the total patient population and each subgroup to sustain a viable commercial business model in U.S. and EU markets.
Biggest changeIf we are successful in obtaining marketing approval from applicable regulatory authorities for AMT-130 or any of our other product candidates, our ability to generate revenues from our product candidates will depend on our success in: ● actual receipt and maintenance of marketing approvals from applicable regulatory authorities; ● launch of commercial sales of our products, if approved, whether alone or in collaboration with others; ● maintaining regulatory approvals, including manufacturing approvals for our third-party manufacturing sites; ● complying with any applicable post-approval commitments and requirements, and maintaining a continued acceptable overall safety profile; ● identifying and engaging effective distributors or resellers on acceptable terms in jurisdictions where we plan to utilize third parties for the marketing and sales of our product candidates; ● acceptance of our products, if approved, by patients, the medical community, and third-party payers; ● effectively competing with existing therapies and gene therapies based on safety and efficacy profiles; ● the strength of our marketing and distribution; ● the achievement optimal pricing based on durability of expression, safety, and efficacy; ● the ultimate content of the regulatory authority approved label, including the approved clinical indications, and any limitations or warnings; ● any distribution or use restrictions imposed by regulatory authorities; ● the interaction of our products with any other medicines that patients may be taking or the restriction on the use of our products with other medicines; ● the standard of care at the time of product approval; ● the relative convenience and ease of administration of our products; ● obtaining healthcare coverage and adequate reimbursement of our products; ● any price concessions, rebates, or discounts we may need to provide; ● obtaining adequate reimbursement for the total patient population and each subgroup to sustain a viable commercial business model in U.S. and EU markets; and ● obtaining and maintaining patent and trade secret protection and non-patent, exclusivities for our product candidates. ​ 56 ​ Table of Contents Even if our product candidates are approved, they may be subject to limitations that make commercialization difficult, and we may experience these difficulties regardless of whether we choose to commercialize our product candidates alone or with a partner.
If we or our contract manufacturers cannot successfully manufacture material that conforms to our specifications and the strict regulatory requirements of the FDA or other regulatory bodies, we will not be able to obtain and/or maintain regulatory approval for our products manufactured by third parties.
If our contract manufacturers cannot successfully manufacture material that conforms to our specifications and the strict regulatory requirements of the FDA or other regulatory bodies, we will not be able to obtain and/or maintain regulatory approval for our products manufactured by third parties.
Our existing loan obligations, together with other similar obligations that we may incur in the future, could have significant adverse consequences, including: ● requiring us to dedicate a portion of our cash resources to the payment of interest and principal, reducing money available to fund working capital, capital expenditures, research and development and other general corporate purposes; ● increasing our vulnerability to adverse changes in general economic, industry and market conditions; ● subjecting us to restrictive covenants that may reduce our ability to take certain corporate actions or obtain further debt or equity financing; ● limiting our flexibility in planning for, or reacting to, changes in our business and the industry in which we compete; and ● placing us at a disadvantage compared to our competitors that have less debt or better debt servicing options.
Our existing loan obligations with Hercules, together with other similar obligations that we may incur in the future, could have significant adverse consequences, including: ● requiring us to dedicate a portion of our cash resources to the payment of interest and principal, reducing money available to fund working capital, capital expenditures, research and development and other general corporate purposes; ● increasing our vulnerability to adverse changes in general economic, industry and market conditions; ● subjecting us to restrictive covenants that may reduce our ability to take certain corporate actions or obtain further debt or equity financing; ● limiting our flexibility in planning for, or reacting to, changes in our business and the industry in which we compete; and ● placing us at a disadvantage compared to our competitors that have less debt or better debt servicing options.
For example: ● others may be able to make gene therapy products that are similar to our product candidates or utilize similar gene therapy technology but that are not covered by the claims of the patents that we own or have licensed; ● we or our licensors or future collaborators might not have been the first to make the inventions covered issued patents or pending patent applications that we own or have licensed; ● we or our licensors or future collaborators might not have been the first to file patent applications covering certain of our inventions; ● others may independently develop similar or alternative technologies or duplicate any of our technologies without infringing our intellectual property rights; ● it is possible that our pending patent applications will not lead to issued patents; ● issued patents that we own or have licensed may be held invalid or unenforceable, as a result of legal challenges by our competitors; ● our competitors might conduct activities in countries where we do not have patent rights and then use the information learned from such activities to develop competitive products for sale in our major commercial markets; ● we may not develop additional proprietary technologies that are patentable; and ● the patents of others may have an adverse effect on our business. 66 ​ Table of Contents The occurrence of any of these events could seriously harm our business.
For example: ● others may be able to make gene therapy products that are similar to our product candidates or utilize similar gene therapy technology but that are not covered by the claims of the patents that we own or have licensed; ● we or our licensors or future collaborators might not have been the first to make the inventions covered issued patents or pending patent applications that we own or have licensed; ● we or our licensors or future collaborators might not have been the first to file patent applications covering certain of our inventions; ● others may independently develop similar or alternative technologies or duplicate any of our technologies without infringing our intellectual property rights; ● it is possible that our pending patent applications will not lead to issued patents; ● issued patents that we own or have licensed may be held invalid or unenforceable, as a result of legal challenges by our competitors; ● our competitors might conduct activities in countries where we do not have patent rights and then use the information learned from such activities to develop competitive products for sale in our major commercial markets; ● we may not develop additional proprietary technologies that are patentable; and ● the patents of others may have an adverse effect on our business. 68 ​ Table of Contents The occurrence of any of these events could seriously harm our business.
Biologics studied for their safety and effectiveness in treating serious or life-threatening illnesses and that provide meaningful therapeutic benefit over existing treatments may 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.
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.
The relatively small market size for orphan indications and the potential for long-term therapeutic benefit from a single administration present challenges to pricing review and negotiation of our product candidates for which we may obtain marketing authorization. Most of our product candidates target rare diseases with relatively small patient populations.
The relatively small market size for orphan indications and the potential for long-term therapeutic benefit from a single administration present challenges for pricing review and negotiation of our product candidates for which we may obtain marketing authorization. Most of our product candidates target rare diseases with relatively small patient populations.
While we have implemented security measures to protect our information technology systems and infrastructure, there can be no assurance that such measures will prevent service interruptions or security breaches that could adversely affect our business and the further development and commercialization of our product and product candidates could be delayed.
While we have implemented security measures designed to protect our information technology systems and infrastructure, there can be no assurance that such measures will prevent service interruptions or security breaches that could adversely affect our business and the further development and commercialization of our product and product candidates could be delayed.
To meet our expected future production needs and our regulatory filing timelines for gene therapy product candidates, we will need to complete the validation of our manufacturing processes and methods for each program, and we may need to develop and validate new or larger scale manufacturing processes and methods.
To meet our expected future production needs and our regulatory filing timelines for gene therapy product candidates, Genezen will need to complete the validation of our manufacturing processes and methods for each program, and we may need to develop and validate new or larger scale manufacturing processes and methods to meet our needs.
Accordingly, actions taken by any of our partners could materially and adversely impact our business. Risks Related to Commercialization If we, or our commercial partners, are unable to successfully commercialize our product candidates or experience significant delays in doing so, our business could be materially harmed.
Accordingly, actions taken by any of our partners could materially and adversely impact our business. Risks Related to Commercialization If we are unable to successfully commercialize our product candidates or experience significant delays in doing so, our business could be materially harmed.
Negative public opinion and increased regulatory scrutiny of gene therapy and genetic research may damage public perception of our product candidates or adversely affect our ability to conduct our business or obtain marketing approvals for our product candidates. Gene therapy remains a novel technology.
Negative public opinion and increased regulatory scrutiny of gene therapy and genetic research may damage the public perception of our product candidates or adversely affect our ability to conduct our business or obtain marketing approvals for our product candidates. Gene therapy remains a novel technology.
These problems include difficulties with production costs and yields, quality control, including stability and potency of the product, quality assurance testing, operator error, shortages of qualified personnel, as well as compliance with strictly enforced federal, state, and foreign regulations.
These problems include difficulties with production costs and yields, quality control, including stability and potency of the product, quality assurance testing, instances of operator error, shortages of qualified personnel, as well as compliance with strictly enforced federal, state, and foreign regulations.
We seek to protect our proprietary technology in part by entering into confidentiality agreements and, if applicable, materials transfer agreements, collaborative research agreements, consulting agreements or other similar agreements with our collaborators, advisors, and consultants prior to beginning research or disclosing proprietary information.
We seek to protect our proprietary technology in part by entering into confidentiality agreements and, if applicable, materials transfer agreements, collaborative research agreements, consulting agreements or other similar agreements with our collaborators, advisors, and consultants prior to beginning research or disclosing confidential or proprietary information.
Issues with any of our manufacturing processes, even minor deviations from our standard processes, could result in insufficient yield, product deficiencies or manufacturing failures that result in adverse patient reactions, lot failures, insufficient inventory, product recalls and product liability claims.
Issues with any of our manufacturing processes, even minor deviations from our standard processes, could result in insufficient yield, product deficiencies or manufacturing or supply failures that could result in adverse patient reactions, lot failures, insufficient inventory, product recalls and product liability claims.
Any information we determine not to disclose may ultimately be deemed significant by you or others with respect to future decisions, conclusions, views, activities or otherwise regarding a particular product candidate or our business.
Any information we determine not to disclose may ultimately be deemed significant by others with respect to future decisions, conclusions, views, activities or otherwise regarding a particular product candidate or our business.
An adverse result in any litigation proceeding could put one or more of our patents at risk of being invalidated, maintained in a more narrowly amended form or interpreted narrowly. ​ 64 ​ Table of Contents Even if resolved in our favor, litigation or other legal proceedings relating to intellectual property claims may cause us to incur significant expenses, increase our operating losses, reduce available resources, and could distract our technical and management personnel from their normal responsibilities.
An adverse result in any litigation proceeding could put one or more of our patents at risk of being invalidated, maintained in a more narrowly amended form or interpreted narrowly. 66 ​ Table of Contents Even if resolved in our favor, litigation or other legal proceedings relating to intellectual property claims may cause us to incur significant expenses, increase our operating losses, reduce available resources, and could distract our technical and management personnel from their normal responsibilities.
We currently rely, and expect to continue to rely, on third parties for the production of some of our preclinical study and planned clinical trial materials and, therefore, we can control only certain aspects of their activities.
We currently rely, and expect to continue to rely, on third parties for the production of our preclinical study and planned clinical trial materials and, therefore, we can control only certain aspects of their activities.
Among other things, the IRA requires manufacturers of certain drugs to engage in price negotiations with Medicare (with the maximum fair prices for the first year of the negotiation program being initially applicable in 2026), with prices that can be negotiated subject to a cap; imposes rebates for certain drugs under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation (first due in 2023); and replaces the Part D coverage gap discount program with a new discounting program (beginning in 2025).
Among other things, the IRA requires manufacturers of certain high-Medicare spend drugs to engage in price negotiations with Medicare (with the maximum fair prices for the first year of the negotiation program being initially applicable in 2026), with prices that can be negotiated subject to a cap; imposes rebates for certain drugs under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation (first due in 2023); and replaces the Part D coverage gap discount program with a new discounting program (beginning in 2025).
Termination of these agreements or reduction or elimination of our rights under these agreements may result in our having to negotiate new or amended agreements with less favorable terms or cause us to lose our rights under these agreements, including our rights to important intellectual property or technology. 63 ​ Table of Contents If we are unable to obtain and maintain patent protection for our technology and products, or if the scope of the patent protection is not sufficiently broad, our ability to successfully commercialize our products may be impaired.
Termination of these agreements or reduction or elimination of our rights under these agreements may result in our having to negotiate new or amended agreements with less favorable terms or cause us to lose our rights under these agreements, including our rights to important intellectual property or technology. 65 ​ Table of Contents If we are unable to obtain and maintain patent protection for our technology and products, or if the scope of the patent protection is not sufficiently broad, our ability to successfully commercialize our products may be impaired.
To the extent that our employees, consultants, or contractors use technology or know-how owned by third parties in their work for us, disputes may arise between us and those third parties as to the rights in related inventions. ​ ​ 65 ​ Table of Contents Adequate remedies may not exist in the event of unauthorized use or disclosure of our confidential information including a breach of our confidentiality agreements.
To the extent that our employees, consultants, or contractors use technology or know-how owned by third parties in their work for us, disputes may arise between us and those third parties as to the rights in related inventions. 67 ​ Table of Contents Adequate remedies may not exist in the event of unauthorized use or disclosure of our confidential information including a breach of our confidentiality agreements.
If an event of default occurs and the lender accelerates the amounts due, we may not be able to make accelerated payments, and the lender could seek to enforce security interests in the collateral securing such indebtedness, which includes substantially all our assets. Our 2023 Amended Facility bears a variable interest rate with a fixed floor. The U.S.
If an event of default occurs and the lender accelerates the amounts due, we may not be able to make accelerated payments, and the lender could seek to enforce security interests in the collateral securing such indebtedness, which includes substantially all our assets. Our 2024 Amended Facility bears a variable interest rate with a fixed floor. The U.S.
Regulatory authorities in some jurisdictions, including the U.S. and the European Union, may designate drugs for relatively small patient populations as orphan drugs. While certain of our product candidates, including AMT-130 have received orphan drug designation, there is no guarantee that we will be able to receive such designations in the future.
Regulatory authorities in some jurisdictions, including the U.S. and the European Union, may designate drugs for relatively small patient populations as orphan drugs. While certain of our product candidates, including AMT-130, AMT-191 and AMT-162 have received orphan drug designation, there is no guarantee that we will be able to receive such designations in the future.
Any approved gene therapy we seek to offer may fail to achieve the degree of market acceptance by physicians, patients, third party payers and others in the medical community necessary for commercial success. Doctors may be reluctant to accept gene therapy as a treatment option or, where available, choose to continue to rely on existing treatments.
Any approved gene therapy we seek to commercialize may fail to achieve the degree of market acceptance by physicians, patients, third party payers and others in the medical community necessary for commercial success. Doctors may be reluctant to accept gene therapy as a treatment option or, where available, choose to continue to rely on existing treatments.
The in-licensing and acquisition of gene therapy technologies is a competitive area, and many more established companies are also pursuing strategies to license or acquire product candidates or technologies that we may consider attractive. These established companies may have a competitive advantage over us due to their size, cash resources and greater clinical development and commercialization capabilities.
The in-licensing and acquisition of gene therapy technologies is a competitive area, and many more established companies are also pursuing strategies to license or acquire product candidates or technologies that we may consider attractive. These established companies may have a competitive advantage over us due to their size, cash resources or superior clinical development and commercialization capabilities.
A small number of patients have experienced serious adverse events during our clinical trials of AMT-060 (HEMGENIX®), etranacogene dezaparvovec (AMT-061), and AMT-130.
A small number of patients experienced serious adverse events during our clinical trials of AMT-060 (HEMGENIX®), etranacogene dezaparvovec (AMT-061), and AMT-130.
The size and complexity of our information technology systems, and those of our collaborators, contractors and consultants, and the large amounts of confidential information stored on those systems, make such systems vulnerable to service interruptions or to security breaches from inadvertent or intentional actions by our employees, third-party vendors and/or business partners, or from cyber-attacks by malicious third parties.
The size and complexity of our information technology systems, and those of our collaborators, third-party vendors, contractors and consultants, and the large amounts of proprietary and confidential information stored on these systems, make such systems vulnerable to service interruptions or to security breaches from inadvertent or intentional actions by our employees, third-party vendors and/or business partners, or from cyber-attacks by malicious third parties.
We may not have sufficient funds and may be unable to arrange for additional financing to pay the amounts due under our existing loan obligations. Failure to make payments or comply with other covenants under 2023 Amended Facility could result in an event of default and acceleration of amounts due.
We may not have sufficient funds and may be unable to arrange for additional financing to pay the amounts due under our existing loan obligations. Failure to make payments or comply with other covenants under 2024 Amended Facility could result in an event of default and acceleration of amounts due.
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 require that this confirmatory trial be commenced prior to FDA granting a product accelerated approval.
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 we were required to, or if we chose to, discontinue development of AMT-130 or any other 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. ​ 43 ​ Table of Contents 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.
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. ​ 40 ​ Table of Contents 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.
Our ability to obtain additional debt financing may be limited by covenants we have made under our 2023 Amended Facility with Hercules and our pledge to Hercules of substantially all our assets as collateral. Our ability to obtain additional equity financing may be limited by our shareholders’ willingness to approve the issuance of additional share capital.
Our ability to obtain additional debt financing may be limited by covenants we have made under our 2024 Amended Facility with Hercules and our pledge to Hercules of substantially all our assets as collateral. Our ability to obtain additional equity financing may be limited by our shareholders’ willingness to approve the issuance of additional share capital.
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’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 Agreement, could affect CSL Behring’s successful commercialization of HEMGENIX® and, in turn, could negatively impact our financial position.
Failure to comply with any of these requirements could result in regulatory, administrative, or other enforcement action, which would be detrimental to our business. 56 ​ Table of Contents For instance, the FDA and other government agencies closely regulate the post-approval marketing and promotion of approved products, including off-label promotion, industry-sponsored scientific and educational activities, and on the Internet and social media.
Failure to comply with any of these requirements could result in regulatory, administrative, or other enforcement action, which would be detrimental to our business. For instance, the FDA and other government agencies closely regulate the post-approval marketing and promotion of approved products, including off-label promotion, industry-sponsored scientific and educational activities, and on the Internet and social media.
In addition, the laws of foreign countries may not protect our rights to the same extent as the laws of the U.S. For example, EU patent law with respect to the patentability of methods of treatment of the human body is more limited than U.S. law.
In addition, the laws of foreign jurisdictions may not protect our rights to the same extent as the laws of the U.S. For example, EU patent law with respect to the patentability of methods of treatment of the human body is more limited than U.S. law.
U.S. holders are urged to consult their tax advisors with respect to the purchase, ownership and disposition of our shares, the possible implications to them of us being treated as a PFIC (including the availability of applicable election, whether making any such election would be advisable in their particular circumstances) as well as the federal, state, local and foreign tax considerations applicable to such holders in connection with the purchase, ownership, and disposition of our shares.
U.S. holders are urged to consult their tax advisors with respect to the purchase, ownership and disposition of our ordinary shares, the possible implications to them of our being treated as a PFIC (including the availability of applicable elections, and whether making any such election would be advisable in their particular circumstances) as well as the U.S. federal, state, local and foreign tax considerations applicable to such holders in connection with the purchase, ownership and disposition of our ordinary shares.
If our understanding and use of biomarkers is inaccurate or flawed, or if our reliance on specific biomarkers such as NfL and mHTT is otherwise misplaced, then we may fail to realize any benefits from using these data and may also be led to invest time and financial resources inefficiently in attempting to develop inappropriate drug candidates. ​ 47 ​ Table of Contents We may not be successful in our efforts to use our gene therapy technology platform to build a pipeline of additional product candidates or otherwise leverage our research and technology to remain competitive.
If our understanding and use of biomarkers is inaccurate or flawed, or if our reliance on specific biomarkers such as CSF NfL is otherwise misplaced, then we may fail to realize any benefits from using these data and may also be led to invest time and financial resources inefficiently in attempting to develop inappropriate drug candidates. 45 ​ Table of Contents We may not be successful in our efforts to use our gene therapy technology platform to build a pipeline of additional product candidates or otherwise leverage our research and technology to remain competitive.
Congressional inquiries and proposed and enacted federal and state legislation designed to, among other things, bring more transparency to drug pricing, reduce the cost of prescription drugs under government payor programs, and review the relationship between pricing and manufacturer patient assistance programs. Most recently, on August 16, 2022, the Inflation Reduction Act of 2022, or IRA, was signed into law.
Congressional inquiries and proposed and enacted federal and state legislation designed to, among other things, bring more transparency to drug pricing, reduce the cost of prescription drugs under government payor programs, and review the relationship between pricing and manufacturer patient assistance programs. Most recently, on August 16, 2022, the Inflation Reduction Act of 2022 (“IRA”), was signed into law.
Failure to secure any necessary financing in a timely manner or on favorable terms could have a material adverse effect on our operations, financial condition or stock price or could require us to delay or abandon development or commercialization plans.
Failure to secure any necessary financing in a timely manner or on favorable terms could have a material adverse effect on our operations, financial condition or share price or could require us to delay or abandon development or commercialization plans.
We rely on third parties, study sites, and others to conduct, supervise, and monitor our preclinical and clinical trials for our product candidates and do not currently plan to independently conduct clinical or preclinical trials of any other potential product candidates.
We rely on third parties, study sites, and others to conduct, supervise, manufacture materials for and monitor our preclinical and clinical trials for our product candidates and do not currently plan to independently conduct clinical or preclinical trials of any other potential product candidates.
The disclosure of our trade secrets or the independent development of our trade secrets by a competitor or other third party would impair our competitive position and may materially harm our business, financial condition, results of operations, stock price and prospects.
The disclosure of our trade secrets or the independent development of our trade secrets by a competitor or other third party would impair our competitive position and may materially harm our business, financial condition, results of operations, share price and prospects.
Under the 2023 Amended Facility, the occurrence of an event that would reasonably be expected to have a material adverse effect on our business, operations, assets, or condition is an event of default.
Under the 2024 Amended Facility, the occurrence of an event that would reasonably be expected to have a material adverse effect on our business, operations, assets, or condition is an event of default.
AMT-260 is being developed based on exclusive licenses to certain patents uniQure France obtained from two French research institutions that continue to collaborate with us. uniQure France also obtained an exclusive license from Regenxbio, Inc. to use AAV9 in connection with the delivery of any sequence that affects the expression of the GRIK2 gene in humans.
AMT-260 is being developed based on exclusive licenses to certain patents uniQure France obtained from two French research institutions. uniQure France also obtained an exclusive license from Regenxbio, Inc. to use AAV9 in connection with the delivery of any sequence that affects the expression of the GRIK2 gene in humans.
The inability to obtain or failure to maintain adequate product exclusivity for our product candidates could have a material adverse effect on our business prospects, results of operations and financial condition. 55 ​ Table of Contents Our focus on developing gene therapies makes it difficult to determine the availability and utility of the orphan drug regime to our product candidates.
The inability to obtain or failure to maintain adequate product exclusivity for our product candidates could have a material adverse effect on our business prospects, results of operations and financial condition. Our focus on developing gene therapies makes it difficult to determine the availability and utility of the orphan drug regime to our product candidates.
Additionally, the patent prosecution process is expensive, time-consuming, and uncertain, and in certain instances we have chosen, and in the future we may choose, not to file and prosecute all necessary or desirable patent applications.
Additionally, the patent prosecution process is expensive, time-consuming, and uncertain, and in certain instances we have chosen, and in the future we may choose, not to file and prosecute all desirable patent applications.
We expect to incur significant expenses in connection with our ongoing activities and we will need to obtain substantial additional funding in order to fund the development of our product pipeline and support our continuing operations.
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.
As a result, if these shareholders were to choose to act together, they may be able, as a practical matter, to control many matters submitted to our shareholders for approval, as well as our management and affairs.
As a result, if these shareholders were to choose to act together, they may be able, as a practical matter, to influence many matters submitted to our shareholders for approval, as well as our management and affairs.
The Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act, or the PPACA, is a sweeping measure intended to, among other things, expand healthcare coverage within the U.S., primarily through the imposition of health insurance mandates on employers and individuals and expansion of the Medicaid program.
The Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act (the “PPACA”), is a sweeping measure intended to, among other things, expand healthcare coverage within the U.S., primarily through the imposition of health insurance mandates on employers and individuals and expansion of the Medicaid program.
Our future profitability may depend, in part, on our ability to commercialize current or future drug candidates in foreign markets for which we may rely on collaboration s with third parties. We are not permitted to market or promote any of our drug candidates before we receive regulatory approval from the applicable regulatory authority in that foreign market.
Our future profitability may depend, in part, on our ability to commercialize current or future drug candidates in foreign markets for which we may rely on collaborations with third parties. We are not permitted to market or promote any of our drug candidates before we receive regulatory approval from the applicable regulatory authority in that foreign market.
In addition to AMT-130, we are also developing other investigational gene therapies, including AMT-260 for the treatment of MTLE, AMT-162 for the treatment of SOD1 ALS and AMT-191 for the treatment of Fabry’s disease.
In addition to AMT-130, we are also developing other investigational gene therapies, including AMT-260 for the treatment of mTLE, AMT-162 for the treatment of SOD1-ALS and AMT-191 for the treatment of Fabry disease.
We expect to continue to rely on third parties, such as CROs, clinical data management organizations, medical and scientific institutions, and clinical and preclinical investigators, to conduct our preclinical studies and clinical trials. While we have agreements governing the activities of such third parties, we have limited influence and control over their actual performance and activities.
We expect to continue to rely on third parties, such as CROs, clinical data management organizations, medical and scientific institutions, and clinical and preclinical investigators, to conduct our preclinical studies and clinical trials. 62 ​ Table of Contents While we have agreements governing the activities of such third parties, we have limited influence and control over their actual performance and activities.
If and to the extent that the Dutch court finds that the jurisdiction of the U.S. court has been based on grounds which are internationally acceptable and that proper legal procedures have been observed, the Dutch court will, in principle, give binding effect to the judgment of the U.S. court, unless such judgment contravenes principles of public policy of the Netherlands.
If and to the extent that the Dutch court finds that the jurisdiction of the U.S. court has been based on grounds which are internationally acceptable and that proper legal procedures have been observed, the Dutch court will, in principle, give binding effect to the judgment of the U.S. court, unless such judgment contravenes Dutch public policy ( ordre public ).
As a result, it may not be possible for shareholders to effect service of process within the U.S. upon such persons or to enforce judgments against them or us in U.S. courts, including judgments predicated upon the civil liability provisions of the federal securities laws of the U.S.
As a result, it may not be possible for shareholders to effect service of process within the U.S. upon such persons or to enforce judgments against them or us in U.S. courts, including judgments predicated upon the civil liability provisions of the federal securities laws 78 ​ Table of Contents of the U.S.
The U.S. and the Netherlands currently do not have a treaty providing for the reciprocal recognition and enforcement of judgments, other than arbitration awards, in civil and commercial matters.
The U.S. and the Netherlands currently do not have a treaty providing for the automatic recognition and enforcement of judgments, other than arbitration awards, in civil and commercial matters.
We are a public company ( naamloze vennootschap ) organized under the laws of the Netherlands and our corporate affairs are governed by our articles of association and by the laws governing companies incorporated in the Netherlands.
We are a public limited liability company ( naamloze vennootschap ) organized under the laws of the Netherlands and our corporate affairs are governed by our articles of association and by the laws governing companies incorporated in the Netherlands.
Events that may prevent successful or timely completion of clinical development, as well as product candidate approval, include, but are not limited to: ● occurrence of serious adverse events associated with a product candidate that are viewed to outweigh its potential benefits; ● insufficient number of patients treated with the product candidate or study period for assessing the effectiveness of the product candidate insufficient in length to assess potential clinical development; ● failures or delays in reaching agreement with regulatory agencies on study design, particularly with respect to our novel gene therapies for which regulatory pathways remain untested; ● failures or delays in hiring sufficient personnel with the requisite expertise to execute multiple clinical programs simultaneously; ● failures or delays in reaching agreement on acceptable terms with clinical research organizations (“CROs”) and clinical trial sites; ● failures or delays in patient recruiting into clinical trials or in the addition of new investigators; ● 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; ● requirements of regulatory authorities, IRBs, or IBCs to modify a study in such a way that it makes the study impracticable to conduct; ● regulatory authority requirements to perform additional or unanticipated clinical trials or testing; ● changes in standards of care which may necessitate the modification of our clinical trials or the conduct of new trials; ● regulatory authority refusal to accept data from foreign clinical study sites; ● disagreements with regulatory authorities regarding our study design, including endpoints, our chosen indication, our chosen bases for comparison as it relates to clinical efficacy, our interpretation of data from preclinical studies and clinical trials or a finding that a product candidate’s benefits do not outweigh its safety risks; ● recommendations from 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; ● suspension or termination of clinical research for various reasons, including noncompliance with regulatory requirements or a finding that the participants are being exposed to unacceptable health risks, undesirable side effects, or other unexpected characteristics (alone or in combination with other products) of the product candidate, or due to findings of undesirable effects caused by a chemically or mechanistically similar therapeutic or therapeutic candidate; ● failure by CROs, other third parties or us to adhere to clinical trial requirements or otherwise properly manage the clinical trial process, including meeting applicable timelines, properly documenting case files, including the retention of proper case files, and properly monitoring and auditing clinical sites; ● failure of sites or clinical investigators to perform in accordance with Good Clinical Practice or applicable regulatory guidelines in other countries; ● failure of patients to abide by clinical trial requirements; 44 ​ Table of Contents ● delays or deviations in the testing, validation, manufacturing, and delivery of our product candidates to the clinical sites; ● delays in having patients complete participation in a study or return for post-treatment follow-up; ● clinical trial sites or patients dropping out of a study; ● the number of patients required for clinical trials of our product candidates being larger than we anticipate; ● clinical trials producing negative or inconclusive results, or our studies failing to reach the necessary level of statistical significance, requiring that we conduct additional clinical trials or abandon product development programs; ● interruptions in manufacturing clinical supply of our product candidates or issues with manufacturing product candidates that meet the necessary quality requirements; ● unanticipated clinical trial costs or insufficient funding, including paying substantial application user fees; ● emergence of new information about or impacting our product candidates or the field of gene therapy; ● with respect to the product candidates for which we manufacture drug product in-house, determinations that there are issues with our manufacturing facility or process; or ● changes in regulatory requirements and guidance, as well as new, revised, postponed, or frozen regulatory requirements (such as the EU Clinical Trials Regulation), that require amending or submitting new clinical protocols, undertaking additional new tests or analyses, or submitting new types or amounts of clinical data.
Events that may prevent successful or timely completion of clinical development, as well as product candidate approval, include, but are not limited to: ● occurrence of serious adverse events associated with a product candidate that are viewed to outweigh its potential benefits; ● insufficient number of patients treated with the product candidate or an insufficient study period for assessing the effectiveness of the product candidate; ● failures or delays in reaching agreement with regulatory agencies on study design, particularly with respect to our novel gene therapies for which regulatory pathways remain untested; ● failures or delays in hiring sufficient personnel with the requisite expertise to execute multiple clinical programs simultaneously; ● failures or delays in reaching agreement on acceptable terms with clinical research organizations (“CROs”) and clinical trial sites; ● failures or delays in identifying and recruiting patients in our clinical studies; ● 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; ● requirements of regulatory authorities, IRBs, or IBCs to modify a study in such a way that it makes the study impracticable to conduct; ● regulatory authority requirements to perform additional or unanticipated clinical trials or testing; ● changes in standards of care which may necessitate the modification of our clinical trials or the conduct of new trials; ● regulatory authority refusal to accept data from foreign clinical study sites; ● 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; ● imposition of a clinical hold by regulatory agencies after an inspection of our clinical trial operations or trial sites; ● suspension or termination of clinical research for various reasons, including noncompliance with regulatory requirements or a finding that the participants are being exposed to unacceptable health risks, undesirable side effects, or other unexpected characteristics (alone or in combination with other products) of the product candidate, or due to findings of undesirable effects caused by a chemically or mechanistically similar therapeutic or therapeutic candidate; 41 ​ Table of Contents ● failure by CROs, other third parties or us to adhere to clinical trial requirements or otherwise properly manage the clinical trial process, including meeting applicable timelines, properly documenting case files, including the retention of proper case files, and properly monitoring and auditing clinical sites; ● failure of sites or clinical investigators to perform in accordance with Good Clinical Practice or applicable regulatory guidelines in other countries; ● failure of patients to abide by clinical trial requirements; ● delays or deviations in the testing, validation, manufacturing, and delivery of our product candidates to the clinical sites; ● delays in having patients complete participation in a study or return for post-treatment follow-up; ● clinical trial sites or patients dropping out of a study; ● the number of patients required for clinical trials of our product candidates being larger than we anticipate; ● clinical trials producing negative or inconclusive results, or our studies failing to reach the necessary level of statistical significance, requiring that we conduct additional clinical trials or abandon development programs; ● interruptions in manufacturing clinical supply of our product candidates or issues with product candidates failing to meet the necessary quality requirements; ● unanticipated clinical trial costs or insufficient funding, including paying substantial application user fees; ● emergence of new information about or impacting our product candidates or the field of gene therapy; ● determinations that there are issues with our third-party manufacturers or their facilities or processes; or ● changes in regulatory requirements and guidance, as well as new, revised, postponed, or frozen regulatory requirements (such as the EU Clinical Trials Regulation), that require amending or submitting new clinical protocols, undertaking additional new tests or analyses, or submitting new types or amounts of clinical data.
For products that receive a priority review designation, the FDA’s marketing application review goal is shortened to six months, as opposed to ten months under standard review. ​ 54 ​ Table of Contents Designation as a fast-track product, breakthrough therapy, RMAT, PRIME, or priority review product is within the discretion of the regulatory agency.
For products that receive a priority review designation, the FDA’s marketing application review goal is shortened to six months, as opposed to ten months under standard review. Designation as a fast-track product, breakthrough therapy, RMAT, PRIME, or priority review product is within the discretion of the regulatory agency.
Even if there is a commercially viable market, if the level of third-party reimbursement is below our expectations, most patients may not be able to afford treatment with our products and our revenues and gross margins will be adversely affected, and our business will be harmed.
Even if there is a commercially viable market, if the level of third-party reimbursement is below our expectations, most patients may not be able to access treatment with our products and our potential revenues and gross margins will be adversely affected, and our business will be harmed.
Any collaboration we enter into may pose several risks, including the following: ● collaborators have significant discretion in determining the efforts and resources that they will apply to these collaborations; ● we may have limited or no control over the design or conduct of clinical trials sponsored by collaborators; ● we may be hampered from entering into collaboration arrangements if we are unable to obtain consent from our licensors to enter into sublicensing arrangements of technology we have in-licensed; ● if any collaborator does not conduct the clinical trials they sponsor in accordance with regulatory requirements or stated protocols, we will not be able to rely on the data produced in such trials in our further development efforts; ● collaborators may not perform their obligations as expected; ● collaborators may also have relationships with other entities, some of which may be our competitors; ● collaborators may not pursue development and commercialization of any product candidates or may elect not to continue or renew development or commercialization programs based on clinical trial results, changes in the collaborators’ strategic focus or available funding, or external factors, such as an acquisition, that divert resources or create competing priorities; ● collaborators may delay clinical trials, provide insufficient funding for a clinical trial program, stop a clinical trial, or abandon a product candidate, repeat or conduct new clinical trials or require a new formulation of a product candidate for clinical testing; ● collaborators could develop, independently or with third parties, products that compete directly or indirectly with our products or product candidates, if, for instance, the collaborators believe that competitive products are more likely to be successfully developed or can be commercialized under terms that are more economically attractive than ours; ● our collaboration arrangements may impose restrictions on our ability to undertake other development efforts that may appear to be attractive to us; ● product candidates discovered in collaboration with us may be viewed by our collaborators as competitive with their own product candidates or products, which may cause collaborators to cease to devote resources to the commercialization of our product candidates; ● a collaborator with marketing and distribution rights that achieves regulatory approval may not commit sufficient resources to the marketing and distribution of such product or products; ● disagreements with collaborators, including over proprietary rights, contract interpretation or the preferred course of development, could cause delays or termination of the research, development or commercialization of product candidates, lead to additional responsibilities for us, delay or impede reimbursement of certain expenses or result in litigation or arbitration, any of which would be time-consuming and expensive; ● collaborators may not properly maintain or defend our intellectual property rights or may use our proprietary information in such a way as to invite litigation that could jeopardize or invalidate our rights or expose us to potential litigation; 62 ​ Table of Contents ● collaborators may infringe the intellectual property rights of third parties, which may expose us to litigation and potential liability; and ● collaborations may in some cases be terminated for the convenience of the collaborator and, if terminated, we could be required to expend additional funds to pursue further development or commercialization of the applicable product or product candidates.
Any collaboration we enter into may pose risks, including the following: ● collaborators have significant discretion in determining the efforts and resources that they will apply to these collaborations; ● we may have limited or no control over the design or conduct of clinical trials sponsored by collaborators; ● we may be hampered from entering into collaboration arrangements if we are unable to obtain consent from our licensors to enter into sublicensing arrangements of technology we have in-licensed; ● if any collaborator does not conduct the clinical trials they sponsor in accordance with regulatory requirements or stated protocols, we will not be able to rely on the data produced in such trials in our further development efforts; ● collaborators may not perform their obligations as expected; ● collaborators may also have relationships with other entities, some of which may be our competitors; ● collaborators may not pursue development and commercialization of any product candidates or may elect not to continue or renew development or commercialization programs based on clinical trial results, changes in the collaborators’ strategic focus or available funding, or external factors, such as an acquisition, that divert resources or create competing priorities; ● collaborators may delay clinical trials, provide insufficient funding for a clinical trial program, stop a clinical trial, or abandon a product candidate, repeat or conduct new clinical trials or require a new formulation of a product candidate for clinical testing; ● collaborators could develop, independently or with third parties, products that compete directly or indirectly with our products or product candidates, if, for instance, the collaborators believe that competitive products are more likely to be successfully developed or can be commercialized under terms that are more economically attractive than ours; ● our collaboration arrangements may impose restrictions on our ability to undertake other development efforts that may appear to be attractive to us; ● product candidates discovered in collaboration with us may be viewed by our collaborators as competitive with their own product candidates or products, which may cause collaborators to cease to devote resources to the commercialization of our product candidates; ● a collaborator with marketing and distribution rights that achieves regulatory approval may not commit sufficient resources to the marketing and distribution of such product or products; ● disagreements with collaborators, including over proprietary rights, contract interpretation or the preferred course of development, could cause delays or termination of the research, development or commercialization of product candidates, lead to additional responsibilities for us, delay or impede reimbursement of certain expenses or result in litigation or arbitration, any of which would be time-consuming and expensive; ● collaborators may not properly maintain or defend our intellectual property rights or may use our proprietary information in such a way as to invite litigation that could jeopardize or invalidate our rights or expose us to potential litigation; ● collaborators may infringe the intellectual property rights of third parties, which may expose us to litigation and potential liability; and ● collaborations may in some cases be terminated for the convenience of the collaborator and, if terminated, we could be required to expend additional funds to pursue further development or commercialization of the applicable product or product candidates. ​ If any collaboration does not result in the successful research, development and commercialization of products or if a collaborator were to terminate an agreement with us, we may not receive future research funding or milestone or royalty payments under that collaboration, and we may lose access to important technologies and capabilities from the collaboration.
Changes in either the patent laws or interpretation of the patent laws in the European Union, the U.S. or other countries may diminish the value of our patents or narrow the scope of our patent protection.
Changes in either the patent laws or interpretation of the patent laws in the European Union, the U.S. or other jurisdictions may diminish the value of our patents or narrow the scope of our patent protection.
Risks Related to Pricing and Reimbursement We and our commercial partner face uncertainty related to insurance coverage of, and pricing and reimbursement for, HEMGENIX® and other product candidates for which we may receive marketing approval. We anticipate that the cost of treatment using our product candidates will be significant.
We and our commercial partner face uncertainty related to insurance coverage of, and pricing and reimbursement for, HEMGENIX® and other product candidates for which we may receive marketing approval. We anticipate that the cost of treatment using our product candidates, if approved, will be significant.
If these or future oppositions are successful or if we are found to otherwise infringe a third party's intellectual property rights, we could be required to obtain a license from such third party to continue developing and marketing our products and technology. We may not be able to obtain the required license on commercially reasonable terms or at all.
If we are found to otherwise infringe a third party’s intellectual property rights, we could be required to obtain a license from such third party to continue developing and marketing our products and technology. We may not be able to obtain the required license on commercially reasonable terms or at all.
Additional risks associated with the continuing impact of the Reorganization include employee attrition beyond our intended reduction in force and adverse effects on employee morale (which may also be further exacerbated by actual or perceived declining value of equity awards), diversion of management attention, adverse effects to our reputation as an employer (which could make it more difficult for us to hire and retain new employees in the future), potential understaffing and potential failure or delays to meet development targets due to the loss of qualified employees or other operational challenges.
Additional risks associated with the continuing impact of these restructuring efforts include employee attrition beyond our intended reduction in force and adverse effects on employee morale (which may be exacerbated by actual or perceived declining value of equity awards), diversion of management attention, adverse effects to our reputation as an employer (which could make it more difficult for us to hire and retain new employees in the future), potential understaffing and potential failure or delays to meet regulatory or development targets due to the loss of qualified employees or other operational challenges.
If a larger population of patients does not experience positive results during our clinical trials, if the results are not reproducible or if our products show diminishing activity over time, our product candidates may not receive approval from the FDA, EMA or comparable regulatory authorities.
If a larger population of patients does not experience positive results during our clinical trials, if the results are not reproducible or if our products show diminishing activity over time, our product candidates may not receive approval from the FDA, EMA or comparable regulatory authorities, or may have conditional approvals revoked.
Clinical trial sites may not have the adequate infrastructure established to handle the administration of our gene therapy products, related surgeries or other means of product administration, or may have difficulty finding eligible patients to enroll into a clinical trial, which may delay or impede our planned trials.
Clinical trial sites may not have the adequate infrastructure established to handle the administration of our gene therapy products, related surgeries or other means of product administration, or may have difficulty finding eligible patients to enroll into our clinical trials, which may delay or impede our planned trials and development timelines.
These reforms could reduce the ultimate demand for our product candidates or put pressure on our product pricing and could seriously harm our business. ​ 67 ​ Table of Contents In the EU, similar political, economic, and regulatory developments may affect our ability to profitably commercialize our product candidates, if approved.
These reforms could reduce the ultimate demand for our product candidates or put pressure on our product pricing and could seriously harm our business. In the EU, similar political, economic, and regulatory developments may affect our ability to profitably commercialize our product candidates, if approved.
Factors common to the manufacturing process associated with most biologics and drugs could also cause production interruptions for us, including, without limitation, raw materials shortages and other supply chain challenges, raw material failures, limited control over pricing of raw materials, growth media failures, equipment malfunctions, costs associated with servicing real property lease and other contractual obligations, facility contamination, labor problems, natural disasters, disruption in utility services, public health crises, terrorist activities, war or cases of force majeure and acts of God that are beyond our control.
Factors common to the manufacturing process associated with most biologics and drugs could also cause production interruptions for us or our third-party manufacturers, including, without limitation, raw materials shortages and other supply chain challenges, raw material failures, limited control over pricing of raw materials, growth media failures, equipment malfunctions, costs associated with servicing real property lease and other contractual obligations, facility contamination, labor problems, natural disasters, disruption in utility services, public health crises, terrorist activities, war or cases of force majeure and other events beyond our control.
Additionally, we may not be able to scale up some or all our manufacturing processes as necessary and on our desired timelines to meet the demands of our clinical product pipeline, which may result in delays in regulatory approvals, inability to produce sufficient amounts of clinical or commercial product, or otherwise adversely affect our business.
Additionally, we and our third-party manufacturers, including Genezen, may not be able to scale up some or all our manufacturing processes as necessary and on our desired timelines to meet the demands of our clinical product pipeline and regulatory timelines, which may result in delays in regulatory approvals, inability to produce sufficient amounts of clinical or commercial product, or otherwise adversely affect our business.
The risk of cancer remains a concern for gene therapy, and we cannot guarantee that patients treated in any of our planned or future clinical studies will not develop cancer as a result of being treated with our product candidates.
The risk of cancer remains a concern for gene therapy, and we cannot guarantee that patients treated in any of our planned or future clinical studies will not develop cancer or experience other adverse events as a result of being treated with our product candidates.
Moreover, actions taken in connection with the Reorganization to streamline our product portfolio may hamper our ability to remain competitive. Mergers and acquisitions in the pharmaceutical and biotechnology industries may result in more resources being concentrated among a smaller number of our competitors.
Moreover, actions taken in connection with our prior restructuring efforts to streamline our product portfolio may hamper our ability to remain competitive. Mergers and acquisitions in the pharmaceutical and biotechnology industries may result in more resources being concentrated among a smaller number of our competitors.
Even if future operations lead to significant levels of distributable profits, we currently intend those earnings, if any, will be reinvested in our business and that dividends will not be paid until we have an established revenue stream to support continuing dividends.
Even if future operations lead to significant levels of distributable profits, we currently expect those earnings, if any, will be reinvested in our business and that dividends will not be paid until we have an established revenue stream to support paying dividends.
Because our programs are focused on the treatment of patients with rare or orphan or ultra-orphan diseases, our ability to enroll eligible patients in these trials may be limited or slower than we anticipate considering the small patient populations involved and the specific age range required for treatment eligibility in some indications.
Because several of our programs are focused on the treatment of patients with rare or orphan or ultra-orphan diseases, our ability to enroll eligible patients in these trials may be limited or slower than we anticipate considering the small patient populations involved and the age range required for trial eligibility for certain indications.
A corporation organized outside the U.S. generally will be classified as a passive foreign investment company (“PFIC”) for U.S. federal income tax purposes in any taxable year in which at least 75% of its gross income is passive income or on average at least 50% of the gross value of its assets is attributable to assets that produce passive income or are held to produce passive income.
A corporation organized outside the U.S. generally will be classified as a PFIC for U.S. federal income tax purposes in any taxable year in which at least 75% of its gross income is passive income or on average at least 50% of the gross value of its assets is attributable to assets that produce passive income or are held to produce passive income.
Several provisions of the law may affect us and increase certain of our costs. ​ 72 ​ Table of Contents In addition, other legislative changes have been adopted since the PPACA was enacted.
Several provisions of the law may affect us and increase certain of our costs. In addition, other legislative changes have been adopted since the PPACA was enacted.
If we are unable to consistently manufacture our gene therapy product candidates or any approved products in accordance with our pre-specified quality parameters and applicable regulatory standards, it could adversely impact our ability to validate our manufacturing processes and methods, to meet our production needs, to file a BLA or other regulatory submissions, to develop our other proprietary programs, to conserve our cash, or to receive financial payments pursuant to our agreements with third parties.
If Genezen or any other third-party manufacturer we engage is unable to consistently manufacture our gene therapy product candidates or any approved products in accordance with our pre-specified quality parameters and applicable regulatory standards, it could adversely impact our ability to validate our manufacturing processes and methods, to meet our production needs, to timely file a BLA or other regulatory submissions, to develop our other proprietary programs, to conserve our cash, or to receive financial payments pursuant to our agreements with third parties.
This could in turn limit our access to capital markets, harm our results of operations, and lead to a decline in the trading price of our ordinary shares.
This could in turn limit our access to capital markets and our ability to fund our business, harm our results of operations, and could lead to a decline in the trading price of our ordinary shares.
If the market opportunities for our product candidates are smaller than we believe they are, our product revenues may be adversely affected, and our business may suffer. We focus our research and product development on treatments for severe genetic and orphan diseases.
If the market opportunities for our product candidates are smaller than we believe they are, our product revenues may be adversely affected, and our business may suffer. We focus our research and development on product candidates designed to treat severe genetic and orphan diseases.
In the past, we have manufactured certain batches of product candidates intended for nonclinical, clinical and process validation purposes that have not met all our pre-specified quality parameters.
In the past and prior to the Lexington Transaction, we have manufactured certain batches of product candidates intended for nonclinical, clinical and process validation purposes that have not met all our pre-specified quality parameters.
If we are unable to raise capital when needed or on attractive terms, we could be forced to delay, reduce, or further eliminate our research and development programs or any future commercialization efforts, which would have a negative impact on our financial condition, results of operations and cash flows.
If we are unable to raise capital when needed or on attractive terms or successfully pursue strategic partnerships where necessary, we could be forced to delay, reduce, or further eliminate our research and development programs or any future commercialization efforts, which would have a negative impact on our financial condition, results of operations and cash flows.
If our operations, or the activities of our collaborators, distributors or other third-party agents are found to be in violation of any of these laws or any other governmental regulations that may apply to us, we may be subject to significant civil, criminal, and administrative penalties, damages, fines, imprisonment, exclusion from participation in government funded healthcare programs and the curtailment or restructuring of our operations.
If our operations, or the activities of our collaborators, distributors or other third-party agents are found to be in violation of any of these laws or any other governmental regulations that may apply to us, we may be subject to significant civil, criminal, and administrative penalties, damages, fines, imprisonment, exclusion from participation in government funded healthcare programs and the curtailment or restructuring of our operations. 72 ​ Table of Contents Additionally, we are subject to various labor and employment laws and regulations.
Actions that we have taken to restructure our business in alignment with our strategic priorities may not be as effective as anticipated, may not result in cost savings to us and could disrupt our business .
Actions that we have taken or may take in the future to restructure our business in alignment with our strategic priorities may not be as effective as anticipated, may not result in cost savings to us and could disrupt our business .
Accordingly, even if we believe one of our product candidates meets the relevant criteria, the agency may disagree and instead determine not to make such a designation.
Accordingly, even if we believe one of our product candidates (other than AMT-130) meets the relevant criteria, the agency may disagree and instead determine not to make such a designation.
We have in the past entered into, and expect in the future to enter into, collaborations with other companies and academic research institutions with respect to important elements of our development programs.
We have in the past entered into, and expect in the future to enter into, collaborations with other companies and academic research institutions with respect to important elements of our business development strategy or existing development programs.

… 350 more changes not shown on this page.

Item 1C. Cybersecurity

Cybersecurity — threats and controls disclosure

133 edited+73 added−77 removed50 unchanged
Biggest changeWe paid EUR 42.1 million ($49.9 million), net of EUR 2.8 million ($3.3 million) of cash acquired, during the year ended December 31, 2021 to acquire 97.7% of the outstanding ordinary shares of uniQure France SAS on July 30, 2021. ​ ​ ​ ​ ​ ​ ​ ​ 101 ​ Table of Contents ​ Net cash generated from financing activities ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year ended December 31, ​ 2023 2022 2021 ​ ​ (in thousands) Cash flows from financing activities ​ ​ ​ ​ ​ ​ ​ ​ ​ Proceeds from Royalty Financing Agreement, net of debt issuance costs ​ $ 370,062 ​ $ - ​ $ - Contingent consideration milestone payment ​ ​ (7,649) ​ ​ - ​ ​ - Proceeds from issuance of shares related to employee stock option and purchase plans ​ ​ 308 ​ ​ 1,445 ​ ​ 2,798 Proceeds from loan increment, net of debt issuance costs ​ ​ - ​ ​ - ​ ​ 64,067 Proceeds from issuance of ordinary shares, net of issuance costs ​ ​ - ​ ​ - ​ ​ 29,565 Repayment of debt assumed through the acquisition of uniQure France SAS ​ ​ - ​ ​ - ​ ​ (1,572) Net cash generated from financing activities ​ $ 362,721 ​ $ 1,445 ​ $ 94,858 ​ In June 2023, we received $370.1 million net proceeds from the Royalty Financing Agreement.
Biggest changeNet cash generated from / (used in) investing activities ​ In 2024, we generated $163.0 million from our investing activities compared to using $205.7 million in 2023 and $182.7 million in 2022. ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year ended December 31, ​ 2024 2023 2022 ​ ​ (in thousands) Proceeds from maturity of debt securities ​ $ 534,498 ​ $ 167,907 ​ ​ — Investment in debt securities ​ ​ (359,841) ​ ​ (366,439) ​ $ (163,146) Divestment of commercial manufacturing facility ​ ​ (8,321) ​ ​ — ​ ​ — Capital expenditures - European sites ​ ​ (1,783) ​ ​ (3,389) ​ ​ (11,904) Capital expenditures - Lexington site ​ ​ (1,585) ​ ​ (3,765) ​ ​ (5,784) Acquisition of uniQure France SAS, net of cash acquired ​ ​ — ​ ​ — ​ ​ (1,900) Net cash generated from / (used in) investing activities ​ $ 162,968 ​ $ (205,686) ​ $ (182,734) ​ ​ 104 ​ Table of Contents Net cash (used in) / generated from financing activities ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year ended December 31, ​ 2024 2023 2022 ​ ​ (in thousands) Cash flows from financing activities ​ ​ ​ ​ ​ ​ ​ ​ ​ Proceeds from Royalty Financing Agreement, net of debt issuance costs ​ $ - ​ $ 370,062 ​ $ - Proceeds from issuance of shares related to employee stock option and purchase plans ​ ​ 2,123 ​ ​ 308 ​ ​ 1,445 Repayment of long-term debt ​ ​ (53,050) ​ ​ - ​ ​ - Contingent consideration milestone payment ​ ​ (8,559) ​ ​ (7,649) ​ ​ - Net cash (used in) / generated from financing activities ​ $ (59,486) ​ $ 362,721 ​ $ 1,445 ​ In December 2024, following the dosing of the first patient in Phase I/II clinical trial for AMT-260, we made a payment of EUR 30.0 million ($31.5 million) to the former shareholders of uniQure France SAS based on contractually defined milestones.
To defend against, detect and respond to cybersecurity incidents, we, among other things: have enabled regular monitoring of our environment by a combination of external partners and internal security tools, conduct employee trainings, monitor emerging laws and regulations related to data protection and information security and implement appropriate changes. ​ Consistent with our cybersecurity risk management policies and controls, we have prepared an incident response plan with several components, including: (i) engagement of a third party security operations center for regular vulnerability scanning and technical monitoring of our systems, (ii) detection and analysis of cybersecurity incidents that present risk of unauthorized access to company assets, including the escalation and triaging of incidents that present acute risks to our business, (iii) containment, eradication and data recovery, and (iv) post-incident analysis.
To defend against, detect and respond to cybersecurity incidents, we, among other things: have enabled regular monitoring of our environment by a combination of external partners and internal security tools, conduct regular employee trainings, monitor emerging laws and regulations related to data protection and information security and implement appropriate changes. ​ Consistent with our cybersecurity risk management policies and controls, we have prepared and implemented an incident response plan with several components, including: (i) engagement of a third party security operations center for regular vulnerability scanning and technical monitoring of our systems, (ii) detection and analysis of cybersecurity incidents that present risk of unauthorized access to company assets, including the escalation and triaging of incidents that present acute risks to our business, (iii) containment, eradication and data recovery, and (iv) post-incident analysis.
This rule defines internal control over financial reporting as a process designed by, or under the supervision of, a company’s chief executive officer and chief financial officer and effected by our board of directors, management and other personnel, to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for external purposes in accordance with generally accepted accounting principles and includes those policies and procedures that (1) pertain to the maintenance of records that, in reasonable detail, accurately and fairly reflect the transactions and dispositions of the assets of the company; (2) provide reasonable assurance that transactions are recorded as necessary to permit preparation of financial statements in accordance with generally accepted accounting principles, and that receipts and expenditures of the company are being made only in accordance with authorizations of management and directors of the company; and (3) provide reasonable assurance regarding prevention or timely detection of unauthorized acquisition, use, or disposition of our assets that could have a material effect on the financial statements. ​ We assessed the effectiveness of our internal control over financial reporting as of December 31, 2023.
This rule defines internal control over financial reporting as a process designed by, or under the supervision of, a company’s chief executive officer and chief financial officer and effected by our board of directors, management and other personnel, to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for external purposes in accordance with generally accepted accounting principles and includes those policies and procedures that (1) pertain to the maintenance of records that, in reasonable detail, accurately and fairly reflect the transactions and dispositions of the assets of the company; (2) provide reasonable assurance that transactions are recorded as necessary to permit preparation of financial statements in accordance with generally accepted accounting principles, and that receipts and expenditures of the company are being made only in accordance with authorizations of management and directors of the company; and (3) provide reasonable assurance regarding prevention or timely detection of unauthorized acquisition, use, or disposition of our assets that could have a material effect on the financial statements. ​ We assessed the effectiveness of our internal control over financial reporting as of December 31, 2024.
Credit risk arises from cash and cash equivalents and deposits with banks and financial institutions, outstanding receivables and committed transactions with collaboration partners and security deposits paid to landlords. We currently have no wholesale debtors other than CSL Behring. We deposited funds as security to our landlord related to our facility in Amsterdam.
Credit risk arises from cash and cash equivalents and deposits with banks and financial institutions, outstanding receivables and committed transactions with collaboration partners and security deposits paid to landlords. We currently have no debtors other than CSL Behring. We deposited funds as security to our landlord related to our facility in Amsterdam.
Under the terms of the Royalty Financing Agreement, we received an upfront payment of $375.0 million in exchange for the Purchaser’s rights to the lowest royalty tier on CSL Behring’s worldwide net sales of HEMGENIX® for certain current and future royalties due to us.
(the “Purchaser”). Under the terms of the Royalty Financing Agreement, we received an upfront payment of $375.0 million in exchange for the Purchaser’s rights to the lowest royalty tier on CSL Behring’s worldwide net sales of HEMGENIX® for certain current and future royalties due to us.
For a discussion of cybersecurity risks applicable to us, see Part I, Item 1A, Risk Factors , under the heading “Our internal computer systems, or those of our collaborators or other contractors or consultants, may fail or suffer security breaches, which could result in a material disruption of our product development programs” in this Annual Report on Form 10-K. ​ ​ 80 ​ Table of Contents Item 2.
For a discussion of cybersecurity risks applicable to us, see Part I, Item 1A, Risk Factors , under the heading “Our internal computer systems, or those of our collaborators or other contractors or consultants, may fail or suffer security breaches, which could result in a material disruption of our product development programs” in this Annual Report on Form 10-K. ​ ​ 83 ​ Table of Contents Item 2.
Words such as “may,” “expect,” “anticipate,” “estimate,” “intend,” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. ​ Overview ​ We are a leader in the field of gene therapy, seeking to deliver to patients suffering from rare and other devasting diseases single treatments with potentially curative results.
Words such as “may,” “expect,” “anticipate,” “estimate,” “intend,” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. ​ Overview ​ We are a leader in the field of gene therapy, seeking to deliver to patients suffering from rare and other devastating diseases single treatments with potentially curative results.
In our management’s opinion, we have maintained effective internal control over financial reporting as of December 31, 2023, based on criteria established in the COSO 2013 framework. ​ Our independent registered public accounting firm, which has audited the consolidated financial statements included in this Annual Report on Form 10-K, has also issued an audit report on the effectiveness of our internal control over financial reporting as of December 31, 2023.
In our management’s opinion, we have maintained effective internal control over financial reporting as of December 31, 2024, based on criteria established in the COSO 2013 framework. ​ Our independent registered public accounting firm, which has audited the consolidated financial statements included in this Annual Report on Form 10-K, has also issued an audit report on the effectiveness of our internal control over financial reporting as of December 31, 2024.
This graph assumes an investment of $100 after market close on December 31, 2018 in each of our ordinary shares, the NASDAQ Composite Index, and the NASDAQ Biotechnology Index. Pursuant to the applicable SEC rules, all values assume reinvestment of the full amount of all dividends; however, no dividends have been declared on our ordinary shares to date.
This graph assumes an investment of $100 after market close on December 31, 2019 in each of our ordinary shares, the NASDAQ Composite Index, and the NASDAQ Biotechnology Index. Pursuant to the applicable SEC rules, all values assume reinvestment of the full amount of all dividends; however, no dividends have been declared on our ordinary shares to date.
Legal Proceedings. ​ None. ​ Item 4. Mine Safety Disclosures. ​ Not applicable. ​ ​ 81 ​ Table of Contents Part II ​ Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities ​ Our ordinary shares are listed on the Nasdaq Global Select Market under the symbol “QURE”.
Legal Proceedings. ​ None. ​ Item 4. Mine Safety Disclosures. ​ Not applicable. ​ ​ 84 ​ Table of Contents Part II ​ Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities ​ Our ordinary shares are listed on the Nasdaq Global Select Market under the symbol “QURE”.
We are subject to certain covenants under the 2023 Amended Facility and may become subject to covenants under any future indebtedness that could limit our ability to take specific actions, such as incurring additional debt, making capital expenditures, or declaring dividends, which could adversely impact our ability to conduct our business.
We are subject to certain covenants under the debt facility and may become subject to covenants under any future indebtedness that could limit our ability to take specific actions, such as incurring additional debt, making capital expenditures, or declaring dividends, which could adversely impact our ability to conduct our business.
Costs of contract manufacturing revenues has increased in the year ended December 31, 2023 compared to the year ended December 31, 2022 due to the increase in sales of HEMGENIX® and a write-down of inventory that has a cost basis in excess of its expected net realizable value.
Costs of contract manufacturing revenues increased in the year ended December 31, 2023 compared to the year ended December 31, 2022 due to the increase in sales of HEMGENIX® and a write-down of inventory that had a cost basis in excess of its expected net realizable value.
In addition, we also operate approximately 12,000 square feet of multi-use office space in Lexington, Massachusetts, which is subject to a lease that expires in 2030 and may be renewed for one subsequent five-year term. ​ We operate approximately 111,000 square feet (seven floors) of multi-use space in Amsterdam, The Netherlands, which is subject to a lease that, as amended to date, terminates in 2032 with an option to extend the lease in five-year increments.
Properties . ​ We operate approximately 12,000 square feet of multi-use office space in Lexington, Massachusetts, which is subject to a lease that expires in 2030 and may be renewed for one subsequent five-year term. ​ We operate approximately 111,000 square feet (seven floors) of multi-use space in Amsterdam, The Netherlands, which is subject to a lease that, as amended to date, terminates in 2032 with an option to extend the lease in five-year increments.
Controls and Procedures . ​ Evaluation of Disclosure Controls and Procedures ​ Our management, with the participation of our chief executive officer (“CEO”, our principal executive officer) and chief financial officer (“CFO”, our principal financial officer), evaluated the effectiveness of our disclosure controls and procedures (as defined in Rules 13a-15(e) and 15d-15(e) under the Exchange Act) as of December 31, 2023.
Controls and Procedures . ​ Evaluation of Disclosure Controls and Procedures ​ Our management, with the participation of our chief executive officer (“CEO”, our principal executive officer) and chief financial officer (“CFO”, our principal financial officer), evaluated the effectiveness of our disclosure controls and procedures (as defined in Rules 13a-15(e) and 15d-15(e) under the Exchange Act) as of December 31, 2024.
Securities Exchange Act of 1934, as amended (the “Exchange Act”), whether made before or after the date hereof and irrespective of any general incorporation language in any such filing. ​ ​ ​ Item 6. Reserved ​ ​ ​ ​ ​ ​ ​ ​ ​ 83 ​ Table of Contents Item 7.
Securities Exchange Act of 1934, as amended (the “Exchange Act”), whether made before or after the date hereof and irrespective of any general incorporation language in any such filing. ​ Item 6. Reserved ​ ​ ​ ​ ​ ​ 86 ​ Table of Contents Item 7.
This number of holders of record also does not include shareholders whose shares may be held in trust by other entities. ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ 82 ​ Table of Contents Share Performance Graph ​ The following graph compares the performance of our ordinary shares (“QURE”) for the periods indicated with the performance of the NASDAQ Composite Index (“ ˄ IXIC”) and the Nasdaq biotechnology index (“ ˄ NBI”).
This number of holders of record also does not include shareholders whose shares may be held in trust by other entities. ​ Share Performance Graph ​ The following graph compares the performance of our ordinary shares (“QURE”) for the periods indicated with the performance of the NASDAQ Composite Index (“ ˄ IXIC”) and the Nasdaq biotechnology index (“ ˄ NBI”).
Based on such evaluation, our CEO and CFO have concluded that as of December 31, 2023, our disclosure controls and procedures were effective. 105 ​ Table of Contents ​ Management’s Annual Report on Internal Control Over Financial Reporting ​ Our management is responsible for establishing and maintaining adequate internal control over financial reporting, as defined in Rules 13a-15(f) and 15d-15(f) under the Exchange Act.
Based on such evaluation, our CEO and CFO have concluded that as of December 31, 2024, our disclosure controls and procedures were effective. 108 ​ Table of Contents ​ Management’s Annual Report on Internal Control Over Financial Reporting ​ Our management is responsible for establishing and maintaining adequate internal control over financial reporting, as defined in Rules 13a-15(f) and 15d-15(f) under the Exchange Act.
Conversely, if the euro had strengthened 10% against the U.S. dollar with all other variables held constant, pre-tax loss for the year would have been $6.0 million lower (December 31, 2022: pre-tax loss $20.4 million higher), and other comprehensive loss would have been $2.6 million lower (December 31, 2022: $32.1 million lower). ​ We strive to mitigate foreign exchange risk through holding sufficient funds in euro and dollars to finance budgeted cash flows for generally 18 months. ​ The sensitivity in other comprehensive income to fluctuations in exchange rates primarily relates to the translation of the net assets of our Dutch entities from their functional currency euro into our reporting currency U.S. dollar. ​ Price risk ​ The market prices for the provision of preclinical and clinical materials and services, as well as external contracted research, may vary over time. ​ The commercial prices of any of our products or product candidates are currently uncertain. ​ We are not exposed to commodity price risk. ​ We do not hold investments classified as available-for-sale or at fair value through profit or loss; therefore, we are not exposed to equity securities price risk. ​ 103 ​ Table of Contents Interest rate risk ​ Our interest rate risk arises from short- and long-term debt and investment securities. ​ In June 2013, we entered into the Hercules Agreement, which was last amended in May 2023, under which our borrowings bear interest at a variable rate with a fixed floor.
Conversely, if the euro had strengthened 10% against the U.S. dollar with all other variables held constant, pre-tax loss for the year would have been $25.0 million lower (December 31, 2023: pre-tax loss $6.0 million lower), and other comprehensive income would have been $12.1 million lower (December 31, 2023: other comprehensive loss $2.6 million lower). ​ We strive to mitigate foreign exchange risk through holding sufficient funds in euro and dollars to finance budgeted cash flows for generally 18 months. ​ The sensitivity in other comprehensive income to fluctuations in exchange rates primarily relates to the translation of the net assets of our Dutch entities from their functional currency euro into our reporting currency U.S. dollar. ​ Price risk ​ The market prices for the provision of preclinical and clinical materials and services, as well as external contracted research, may vary over time. ​ The commercial prices of any of our products or product candidates are currently uncertain. ​ We are not exposed to commodity price risk. ​ We do not hold investments classified as available-for-sale or at fair value through profit or loss; therefore, we are not exposed to equity securities price risk. ​ Interest rate risk ​ Our interest rate risk arises from short- and long-term debt and investment securities. ​ In June 2013, we entered into the Hercules Agreement, which was last amended in July 2024, under which our borrowings bear interest at a variable rate with a fixed floor.
The performance of our ordinary shares shown on the graph below is not necessarily indicative of the future performance of our ordinary shares. ​ This graph and related information is not “soliciting material,” is not deemed “filed” with the SEC and, except to the extent incorporated by reference, is not to be incorporated by reference into any of our filings under the Securities Act, or the U.S.
The performance of our ordinary shares shown on the graph below is not necessarily indicative of the future performance of our ordinary shares. ​ 85 ​ Table of Contents This graph and related information are not “soliciting material,” is not deemed “filed” with the SEC and, except to the extent incorporated by reference, is not to be incorporated by reference into any of our filings under the Securities Act, or the U.S.
Net cash generated from operating activities also included favorable changes in operating assets and liabilities of $81.1 million. There was a net increase in accounts receivable, prepaid expenses, and other current assets and receivables of $1.3 million.
Net cash generated from operating activities also included favorable changes in operating assets and liabilities of $80.5 million. There was a net increase in accounts receivable, prepaid expenses, and other current assets and receivables of $1.3 million.
Because of its inherent limitations, internal control over financial reporting may not prevent or detect misstatements due to error or fraud. ​ Changes in internal control over financial reporting During the fourth quarter of 2023, there were no changes in our internal control over financial reporting (as defined in Rule 13a-15(f) under the Exchange Act) that materially affected, or are reasonably likely to materially affect, our internal control over financial reporting. ​ ​ ​ ​ ​ ​ ​ 106 ​ Table of Contents ​ Item 9B.
Because of its inherent limitations, internal control over financial reporting may not prevent or detect misstatements due to error or fraud. ​ Changes in internal control over financial reporting During the fourth quarter of 2024, there were no changes in our internal control over financial reporting (as defined in Rule 13a-15(f) under the Exchange Act) that materially affected, or are reasonably likely to materially affect, our internal control over financial reporting. ​ Item 9B.
The timing of achieving these milestones and consequently the timing of payments, as well as whether the milestone will be achieved at all, is generally uncertain. These payments are owed in euro and have been translated at the foreign exchange rate as of December 31, 2023, of $1.10/€1.00.
The timing of achieving these milestones and consequently the timing of payments, as well as whether the milestone will be achieved at all, is generally uncertain. These payments are owed in euro and have been translated at the foreign exchange rate as of December 31, 2024, of $1.04/€1.00.
We incurred significant research and development costs related to manufacturing and other enabling technologies that are applicable across all our programs. Our R&D expenses may vary substantially from period to period based on the timing of our research and development activities, including manufacturing campaigns, regulatory submissions, and enrollment of patients in clinical trials.
We incurred significant research and development costs related to manufacturing prior to the Closing of the Lexington Transaction and other enabling technologies that are applicable across all our programs. Our R&D expenses may vary substantially from period to period based on the timing of our research and development activities, including regulatory submissions, and enrollment of patients in clinical trials.
We anticipate that we will retain all earnings, if any, to support operations and to finance the growth and development of our business for the foreseeable future. ​ Unregistered Sales of Equity Securities ​ During the period covered by this Annual Report on Form 10-K, we have not issued any securities that were not registered under the Securities Act of 1933, as amended (the “Securities Act”). ​ Issuer Share Repurchases ​ We did not make any purchases of our ordinary shares during the period covered by this Annual Report on Form 10-K. ​ Holders ​ As of February 23, 2024, there were approximately six holders of record of our ordinary shares.
We anticipate that we will retain all earnings, if any, to support operations and to finance the growth and development of our business for the foreseeable future. ​ Unregistered Sales of Equity Securities ​ During the period covered by this Annual Report on Form 10-K, we have not issued any securities that were not registered under the Securities Act of 1933, as amended (the “Securities Act”). ​ Issuer Purchases of Equity Securities ​ We did not make any purchases of our ordinary shares during the period covered by this Annual Report on Form 10-K. ​ Holders ​ As of February 24, 2025, there were approximately three holders of record of our ordinary shares.
Estimating the nature, timing, or cost of the development of any of our product candidates involves considerable judgement due to numerous risks and uncertainties associated with developing gene therapies, including the uncertainty of: ● the scope, rate of progress and expense of our research and development activities; ● our ability to successfully manufacture and scale-up production; ● clinical trial protocols, speed of enrollment and resulting data; ● the effectiveness and safety of our product candidates; and ● the timing of regulatory approvals.
Estimating the nature, timing, or cost of the development of any of our product candidates involves considerable judgement due to numerous risks and uncertainties associated with developing gene therapies, including the uncertainty of: ● the scope, rate of progress and expense of our research and development activities; ● clinical trial protocols, speed of enrollment and resulting data; ● the effectiveness and safety of our product candidates; and ● the timing of regulatory approvals.
Due to the high credit quality of our counterparties, we believe there is no material exposure to credit risk in our portfolio of investment securities. ​ Liquidity Risk ​ Based on our current operating plan, research and development plans and our timing expectations related to the progress of our programs and following the Reorganization, we believe that our cash and cash equivalents and investment securities will fund our operations into the second quarter of 2027.
Due to the high credit quality of our counterparties, we believe there is no material exposure to credit risk in our portfolio of investment securities. ​ Liquidity Risk ​ 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 cash and cash equivalents and investment securities will fund our operations through the second half of 2027.
There was a net decrease in accounts payable, accrued expenses, other liabilities, and operating leases of $10.8 million, primarily related to a decrease of $4.2 million in accounts payable and a decrease of $6.6 million related to various accruals. Net cash used in operating activities also includes a payment for a contingent consideration milestone of $1.9 million.
There was a net decrease in accounts payable, accrued expenses, other liabilities, and operating leases of $9.5 million, primarily related to a decrease of $4.2 million in accounts payable and a decrease of $5.3 million related to various accruals. Net cash used in operating activities also includes a payment for a contingent consideration milestone of $1.9 million.
We also have short-term investment securities in U.S. and European government bonds maturing within one to seven months. Our investment policy requires us to invest in U.S. and European government bonds with the highest investment credit rating.
We also have short-term investment securities in U.S. and European government bonds maturing within two to five months. Our investment policy requires us to invest in U.S. and European government bonds with the highest investment credit rating.
As of December 31, 2023, we had an accumulated deficit of $890.4 million. ​ Sources of liquidity ​ From our first institutional venture capital financing in 2006 through the current period, we funded our operations primarily through private and public placements of equity securities, debt securities, payments from our collaboration partners as well as from selling a portion of royalties due from our collaboration partner CSL Behring.
As of December 31, 2024, we had an accumulated deficit of $1,130.0 million. ​ Sources of liquidity ​ From our first institutional venture capital financing in 2006 through the current period, we funded our operations primarily through private and public placements of equity securities, debt securities, payments from our collaboration partners as well as $370.1 million from selling a portion of royalties due from our collaboration partner CSL Behring in 2023.
For example, if we hold a security that was issued at a fixed interest rate at the then-prevailing rate and the prevailing interest rate later rises, the fair value of our investment will probably decline. ​ The duration of all of our investment securities held as of December 31, 2023, was between one to seven months.
For example, if we hold a security that was issued at a fixed interest rate at the then-prevailing rate and the prevailing interest rate later rises, the fair value of our investment will probably decline. ​ The duration of all of our investment securities held as of December 31, 2024, was between two to five months.
Our R&D expenses generally consist of costs incurred for the development of our target candidates, which include: ● employee-related expenses, including salaries, benefits, travel and share-based compensation expense; ● costs incurred for laboratory research, preclinical and nonclinical studies, clinical trials, statistical analysis and report writing, and regulatory compliance costs incurred with clinical research organizations and other third-party vendors; ● costs incurred to conduct consistency and comparability studies; ● costs incurred for the development and improvement of our manufacturing processes and methods; ● costs associated with research activities for enabling technology platforms, such as next-generation vectors, promoters and re-administration of gene therapies; ● costs associated with the rendering of collaboration services; ● payments related to identifiable intangible assets without an alternative future use; ● payments to our licensors for milestones that have been achieved related to our product candidates, including approval of the MAA and BLA for HEMGENIX ® ; ● facilities, depreciation, and other expenses, which include direct and allocated expenses for rent and maintenance of facilities, insurance, and other supplies; and ● changes in the fair value of liabilities recorded in relation to our acquisition of uniQure France SAS. ​ Our research and development expenses primarily consist of costs incurred for the research and development of our product candidates, which include: ​ ● AMT-130 (Huntington’s disease).
Our R&D expenses generally consist of costs incurred for the development of our target candidates, which include: ● employee-related expenses, including salaries, benefits, travel and share-based compensation expense; ● costs incurred for laboratory research, preclinical and nonclinical studies, clinical trials, statistical analysis and report writing, and regulatory compliance costs incurred with clinical research organizations and other third-party vendors; ● costs incurred to conduct consistency and comparability studies; ● costs incurred for the development and improvement of our manufacturing processes and methods; ● costs associated with research activities for enabling technology platforms; ● costs associated with the rendering of collaboration services; ● payments related to identifiable intangible assets without an alternative future use; ● payments to our licensors for milestones that have been achieved related to our product candidates; ● facilities, depreciation, and other expenses, which include direct and allocated expenses for rent and maintenance of facilities, insurance, and other supplies; and ● changes in the fair value of liabilities recorded in relation to our acquisition of uniQure France SAS. ​ ​ 94 ​ Table of Contents Our research and development expenses primarily consist of costs incurred for the research and development of our product candidates, which include: ​ ● AMT-130 (Huntington’s disease).
We recognize license revenue in relation to the License Sale when it becomes probable that regulatory and sales milestone events will be achieved as well as when royalties on sales of Product have been earned. We recognized $2.8 million, $100.0 million and $517.4 million of license revenue for the years ended December 31, 2023, 2022 and 2021, respectively.
We recognize license revenue in relation to the License Sale when it becomes probable that regulatory and sales milestone events will be achieved as well as when royalties on sales of HEMGENIX® have been earned. We recognized $10.1 million, $2.8 million and $100.0 million of license revenue for the years ended December 31, 2024, 2023 and 2022, respectively.
As of December 31, 2023, the loan bore an interest rate of 13.2%. ​ As of December 31, 2023, if interest rates on borrowings had been 1.0% higher with all other variables held constant, pre-tax earnings for the year would have been $1.0 million lower (2022: $1.0 million lower; 2021: $0.7 million lower.) ​ We invest in government debt in accordance with our investment policy.
As of December 31, 2024, the loan bore an interest rate of 12.2%. 106 ​ Table of Contents ​ As of December 31, 2024, if interest rates on borrowings had been 1.0% higher with all other variables held constant, pre-tax earnings for the year would have been $0.8 million lower (2023: $1.0 million lower; 2022: $1.0 million lower.) ​ We invest in government debt in accordance with our investment policy.
Based on our current operating plan, research and development plans and our timing expectations related to the progress of our programs and following the Reorganization, we believe that our cash and cash equivalents and investment securities will fund our operations into second quarter of 2027.
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 cash and cash equivalents and investment securities will fund our operations through the second half of 2027.
As of December 31, 2023, we expect these obligations will become payable between the first half of 2024 and 2031. If and when due, up to 25% of the milestone payments can be settled with our ordinary shares.
As of December 31, 2024, we expect these obligations will become payable between 2029 and 2033. If and when due, up to 25% of the milestone payments can be settled with our ordinary shares.
The commitments include payments related to post-acquisition services that we agreed to as part of the transaction. The timing of achieving these milestones, as well as whether the milestone will be achieved at all, and consequently the timing of payments is generally uncertain.
The commitments include payments related to post-acquisition services that we agreed to as part of the transaction. The timing of achieving these milestones, as well as whether the milestone will be achieved at all, and consequently the timing of payments is generally uncertain. We expect these obligations will become payable between 2029 and 2033.
An increase in the discount rate reduces the fair value of the contingent consideration liability whereas a decrease in the discount rate increases the fair market value of the contingent consideration liability. ● We need to develop an estimate of when a milestone is expected to be achieved.
An increase in the discount rate reduces the fair value of the contingent consideration liability whereas a decrease in the discount rate increases the fair market value of the contingent consideration liability. 90 ​ Table of Contents ● We need to regularly update our estimate of when a milestone is expected to be achieved.
We incurred $0.1 million, $1.3 million and $25.0 million of such cost in the years ended December 31, 2023, 2022 and 2021, respectively. We recognize collaboration revenues associated with services to CSL Behring in accordance with the CSL Behring Agreement. Collaboration revenue related to these contracted services is recognized when the performance obligations are satisfied.
We incurred $1.3 million, $0.1 million and $1.3 million of such cost in the years ended December 31, 2024, 2023 and 2022, respectively. We recognize collaboration revenues associated with services we provide to CSL Behring. Collaboration revenue is recognized when the performance obligations are satisfied.
To the extent we need to finance our cash needs through equity offerings or debt financings, such financing may be subject to unfavorable terms including without limitation, the negotiation and execution of definitive documentation, as well as credit and debt market conditions, and we may not be able to obtain such financing on terms acceptable to us or at all.
The debt facility permits us to issue up to $500.0 million of convertible debt. 102 ​ Table of Contents To the extent we need to finance our cash needs through equity offerings or debt financings, such financing may be subject to unfavorable terms including without limitation, the negotiation and execution of definitive documentation, as well as credit and debt market conditions, and we may not be able to obtain such financing on terms acceptable to us or at all.
We have incurred costs related to the preclinical development of AMT-191 for the treatment of Fabry disease; ● AMT-162 ( Amyotrophic Lateral Sclerosis caused by mutations in SOD1 ) We have incurred costs related to the acquisition in addition to costs incurred to initiate a Phase I/II clinical trial; 91 ​ Table of Contents ● Etranacogene dezaparvovec (hemophilia B) .
We have incurred costs related to the development of AMT-191 for the treatment of Fabry disease; ● AMT-162 ( Amyotrophic Lateral Sclerosis caused by mutations in SOD1 ) We have incurred costs related to the acquisition in addition to costs incurred to initiate and conduct a Phase I/II clinical trial; ● AMT-061 (Hemophilia B) .
On December 31, 2023, if the euro had weakened 10% against the U.S. dollar with all other variables held constant, pre-tax loss for the year would have been $6.0 million higher (December 31, 2022: pre-tax loss $20.4 million lower), and other comprehensive loss would have been $0.3 million higher (December 31, 2022: $24.4 million higher).
On December 31, 2024, if the euro had weakened 10% against the U.S. dollar with all other variables held constant, pre-tax loss for the year would have been $25.0 million higher (December 31, 2023: pre-tax loss $6.0 million higher), and other comprehensive income would have been $11.0 million higher (December 31, 2023: other comprehensive loss $0.3 million higher).
We continue to incur losses in the current period. We recorded a net loss of $308.5 million for the year ended December 31, 2023, and net loss of $126.8 million in 2022, and a net income of $329.6 million in 2021.
We continued to incur losses in the current period. We recorded a net loss of $239.6 million for the year ended December 31, 2024, and net loss of $308.5 million in 2023, and a net loss of $126.8 million in 2022.
Contract manufacturing revenues are realized when earned upon sales of HEMGENIX ® to CSL Behring. We recognized $10.8 million and $1.7 million contract manufacturing revenues in the year ended December 31, 2023 and 2022, respectively.
We recognized contract manufacturing revenues related to contract manufacturing HEMGENIX ® for CSL Behring when earned upon sales of HEMGENIX ® to CSL Behring. We recognized $6.1 million, $10.8 million and $1.7 million contract manufacturing revenues in the years ended December 31, 2024, 2023 and 2022, respectively.
The amounts payable in accordance with the SPA are contingent upon realization of certain milestones associated with the TLE research program. Contingent consideration was measured at fair value at the Acquisition Date with changes in fair value recognized in the consolidated statements of operations in research and development expenses.
The amounts payable in accordance with the share and purchase agreement (“SPA”) are contingent upon realization of certain milestones associated with AMT-260. Contingent consideration was measured at fair value at the Acquisition Date with changes in fair value recognized in the consolidated statements of operations in research and development expenses.
During the year ended December 31, 2021, the loans were repaid in their entirety. ​ Funding requirements ​ Our future capital requirements will depend on many factors, including but not limited to: ● contractual milestone payments and royalties we might be owed in accordance with the CSL Behring Agreement; ​ ● earnout payments we might owe the former shareholders of uniQure France SAS, which are subject to the achievement of specific development and regulatory milestones; ● the scope, timing, results, and costs of our current and planned clinical trials, including those for AMT-130 in Huntington’s disease; ● the scope, obligations and restrictions on our business related to our existing equity, debt or royalty monetization financings and underlying agreements; ● the extent to which we acquire or in-license other businesses, products, product candidates or technologies; ​ ● the amount and timing of revenue, if any, we receive from manufacturing products for CSL Behring; ​ ● the scope, timing, results and costs of preclinical development and laboratory testing of our additional product candidates; ● the need for additional resources and related recruitment costs to support the preclinical and clinical development of our product candidates; ● the need for any additional tests, studies, or trials beyond those originally anticipated to confirm the safety or efficacy of our product candidates and technologies; ● the cost, timing and outcome of regulatory reviews associated with our product candidates; ​ 102 ​ Table of Contents ● our ability to enter into collaboration arrangements in the future; ​ ● the costs and timing of preparing, filing, expanding, acquiring, licensing, maintaining, enforcing, and prosecuting patents and patent applications, as well as defending any intellectual property-related claims; and ● the costs associated with maintaining quality compliance and optimizing our manufacturing processes, including the operating costs associated with our Lexington, Massachusetts manufacturing facility. ​ ​ Item 7A.
Funding requirements ​ Our future capital requirements will depend on many factors, including but not limited to: ● activities related to submission of a BLA for AMT-130 in Huntington’s disease; ● activities to prepare for the commercialization of AMT-130 in Huntington’s disease in the United States; ● investments to launch AMT-130 in Huntington’s disease in the United States including the amounts of revenue we generate following the launch; ● earnout payments we might owe the former shareholders of uniQure France SAS, which are subject to the achievement of specific development and regulatory milestones; ● contractual milestone payments and royalties we might be owed in accordance with the CSL Behring Agreement; ● the scope, timing, results, and costs of our current and planned clinical trials; ● the scope, obligations and restrictions on our business related to our existing equity, debt or royalty monetization financings and underlying agreements; ● the extent to which we acquire or in-license other businesses, products, product candidates or technologies; ● the scope, timing, results and costs of preclinical development and laboratory testing of our additional product candidates; ● the need for additional resources and related recruitment costs to support the preclinical and clinical development of our product candidates; ● the need for any additional tests, studies, or trials beyond those originally anticipated to confirm the safety or efficacy of our product candidates and technologies; ● the cost, timing and outcome of regulatory reviews associated with our product candidates; ● our ability to enter into collaboration arrangements in the future; and ● the costs and timing of preparing, filing, expanding, acquiring, licensing, maintaining, enforcing, and prosecuting patents and patent applications, as well as defending any intellectual property-related claims. ​ 105 ​ Table of Contents Item 7A.
Balances due within 12 months equal their carrying value as the impact of discounting is not significant. ​ ​ ​ 104 ​ Table of Contents ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Less than ​ Between ​ Between ​ ​ ​ ​ ​ Undefined ​ 1 year ​ 1 - 3 years ​ 3 - 5 years ​ Over 5 years ​ ​ (in thousands) At December 31, 2023 ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Long-term debt ​ $ — ​ $ 13,420 ​ $ 134,150 ​ $ — ​ $ — Accounts payable, accrued expenses and other current liabilities ​ — ​ 37,120 ​ — ​ — ​ — Commitments related to acquisition of uniQure France SAS (maximum nominal amounts) (1) ​ 209,707 ​ — ​ — ​ — ​ — Total ​ $ 209,707 ​ $ 50,540 ​ $ 134,150 ​ $ — ​ $ — At December 31, 2022 ​ ​ ​ ​ ​ Long-term debt ​ $ ​ ​ ​ 14,870 ​ ​ 129,622 ​ ​ ​ ​ ​ ​ Accounts payable, accrued expenses and other current liabilities ​ ​ ​ ​ ​ 41,555 ​ ​ ​ ​ ​ ​ ​ ​ ​ Commitments related to acquisition of uniQure France SAS (maximum nominal amounts) (1) ​ 214,070 ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Total ​ $ 214,070 ​ $ 56,425 ​ $ 129,622 ​ $ — ​ $ — ​ (1) Payments are due in EUR and have been translated at the foreign exchange rate as of December 31, 2023, of $1.10 / €1.00 ​ In relation to our acquisition of uniQure France SAS , we entered into commitments to make payments to the former shareholders upon the achievement of certain contractual milestones.
Balances due within 12 months equal their carrying value as the impact of discounting is not significant. ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Less than ​ Between ​ Between ​ ​ ​ ​ ​ Undefined ​ 1 year ​ 1 - 3 years ​ 3 - 5 years ​ Over 5 years ​ ​ (in thousands) At December 31, 2024 ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Long-term debt ​ $ — ​ $ 8,616 ​ $ 57,403 ​ $ — ​ $ — Accounts payable, accrued expenses and other current liabilities ​ — ​ 36,452 ​ — ​ — ​ — Commitments related to acquisition of uniQure France SAS (maximum nominal amounts) (1) ​ 166,195 ​ — ​ — ​ — ​ — Total ​ $ 166,195 ​ $ 45,068 ​ $ 57,403 ​ $ — ​ $ — At December 31, 2023 ​ ​ ​ ​ ​ Long-term debt ​ $ — ​ $ 13,420 ​ $ 134,150 ​ ​ ​ ​ ​ ​ Accounts payable, accrued expenses and other current liabilities ​ ​ — ​ 37,120 ​ — ​ ​ ​ ​ ​ ​ Commitments related to acquisition of uniQure France SAS (maximum nominal amounts) (2) ​ 209,707 ​ — ​ — ​ ​ ​ ​ ​ ​ Total ​ $ 209,707 ​ $ 50,540 ​ $ 134,150 ​ $ — ​ $ — ​ (1) Payments are due in EUR and have been translated at the foreign exchange rate as of December 31, 2024, of $1.04 / €1.00 (2) Payments are due in EUR and have been translated at the foreign exchange rate as of December 31, 2023, of $1.10 / €1.00 ​ In relation to our acquisition of uniQure France SAS , we entered into commitments to make payments to the former shareholders upon the achievement of certain contractual milestones.
Critical Accounting Policies and Estimates ​ In preparing our consolidated financial statements in accordance with U.S. GAAP and pursuant to the rules and regulations promulgated by the SEC we make assumptions, judgments and estimates that can have a significant impact on our net loss/income and affect the reported amounts of certain assets, liabilities, revenue and expenses, and related disclosures.
GAAP and pursuant to the rules and regulations promulgated by the SEC we make assumptions, judgments and estimates that can have a significant impact on our net loss/income and affect the reported amounts of certain assets, liabilities, revenue and expenses, and related disclosures.
We are contractually required to repay the $100.0 million in full in January 2027. Leases We entered into lease arrangements for facilities, including corporate, manufacturing and office space. As of December 31, 2023, we had fixed lease payment obligations of $53.1 million, with $8.3 million payable within 12 months.
We are contractually required to repay the $50.0 million principal outstanding in full in January 2027. Leases We entered into lease arrangements for facilities, including corporate, laboratory and office space. As of December 31, 2024, we had fixed lease payment obligations of $23.0 million, with $4.1 million payable within 12 months.
Changes in contingent consideration can result from changes in the assumed achievement and timing of estimated milestones and the discount rate used to estimate the fair value of the liability: 87 ​ Table of Contents ● We had used discount rates ranging from 14.0% to 14.4% to calculate the contingent consideration as of December 31, 2022.
Changes in contingent consideration can result from changes in the assumed achievement and timing of estimated milestones and the discount rate used to estimate the fair value of the liability: ● We had used discount rates ranging from 15.3% to 15.6% to calculate the contingent consideration as of December 31, 2023.
We recognized $2.8 million of license revenue in 2023 related to royalty payments owed on HEMGENIX® sales, when earned. We recognized $100.0 million of license revenue in 2022 related to a milestone payment following the first sale of HEMGENIX ® in the U.S. in 2023, which we considered probable as of December 31, 2022.
We recognized $10.1 million and $2.8 million of license revenue in 2024 and 2023 related to royalty payments owed on HEMGENIX® sales, when earned. We recognized $100.0 million of license revenue in 2022 related to a milestone payment owed on the first sale of HEMGENIX ® in the U.S. in 2023.
In 2023, we recognized a net foreign currency loss of $1.7 million related to our borrowings from Hercules, the Royalty Financing Agreement and our cash and cash equivalents and investment securities as well as loans between entities within the uniQure group, compared to a net gain of $23.2 million in 2022 and a net gain of $29.7 million in 2021.
In 2024, we recognized a net foreign currency loss of $10.5 million related to our borrowings from Hercules, the May 2023 royalty financing agreement and our cash and cash equivalents and investment securities as well as loans between entities within the uniQure group.
After the Closing, CSL Behring is responsible for the clinical and regulatory development and commercialization of the Product; ● Preclinical research programs . We incurred costs related to the research of multiple preclinical gene therapy product candidates with the potential to treat certain rare and other serious medical conditions; and ● Technology platform development and other related research .
We incurred costs related to the research of multiple preclinical gene therapy product candidates with the potential to treat certain rare and other serious medical conditions; and ● Technology platform development and other related research .
The table below summarizes our consolidated cash flow data for the years ended December 31: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year ended December 31, ​ 2023 2022 2021 ​ ​ (in thousands) Cash, cash equivalents and restricted cash at the beginning of the period ​ $ 231,173 ​ $ 559,353 ​ $ 247,680 Net cash used in operating activities ​ ​ (145,929) ​ ​ (145,060) ​ ​ 287,959 Net cash used in investing activities ​ ​ (205,686) ​ ​ (182,734) ​ ​ (67,387) Net cash generated from financing activities ​ ​ 362,721 ​ ​ 1,445 ​ ​ 94,858 Foreign exchange impact ​ ​ 2,265 ​ ​ (1,831) ​ ​ (3,757) Cash, cash equivalents and restricted cash at the end of period ​ $ 244,544 ​ $ 231,173 ​ $ 559,353 ​ 98 ​ Table of Contents We had previously incurred losses and cumulative negative cash flows from operations since our business was founded by our predecessor entity AMT Holding N.V. in 1998, with the exception of generating income in 2021 after receiving the upfront payment upon Closing of the CSL Behring Agreement.
As of December 31, 2024 our remaining minimum purchase commitments amount to $12.5 million with $4.0 million to be paid within the next 12 months. ​ The table below summarizes our consolidated cash flow data for the years ended December 31: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year ended December 31, ​ 2024 2023 2022 ​ ​ (in thousands) Cash, cash equivalents and restricted cash at the beginning of the period ​ $ 244,544 ​ $ 231,173 ​ $ 559,353 Net cash used in operating activities ​ ​ (182,728) ​ ​ (145,929) ​ ​ (145,060) Net cash generated from / (used in) investing activities ​ ​ 162,968 ​ ​ (205,686) ​ ​ (182,734) Net cash (used in) / generated from financing activities ​ ​ (59,486) ​ ​ 362,721 ​ ​ 1,445 Foreign exchange impact ​ ​ (4,969) ​ ​ 2,265 ​ ​ (1,831) Cash, cash equivalents and restricted cash at the end of period ​ $ 160,329 ​ $ 244,544 ​ $ 231,173 ​ We had previously incurred losses and cumulative negative cash flows from operations since our business was founded by our predecessor entity AMT Holding N.V. in 1998, with the exception of generating income in 2021 after receiving the upfront payment upon Closing of the CSL Behring Agreement.
The interest rate is adjustable and is the greater of (i) 7.95% and (ii) 7.95% plus the prime rate less 3.25% per annum. Under the 2023 Amended Facility, we owe a back-end fee of $4.9 million on December 1, 2025 and a back-end fee of $1.3 million on January 5, 2027.
The interest rate is adjustable and is the greater of (i) 7.95% and (ii) 7.95% plus the prime rate less 3.25% per annum. We owe a back-end fee of $2.4 million on December 1, 2025 and a back-end fee of $0.6 million on the Maturity Date.
The decrease in 2023 of $1.5 million, compared to 2022, is primarily due to forfeitures as a result of the Reorganization and other severance, and a decrease in the fair value of awards granted.
The decrease in 2023 of $1.5 million, compared to 2022, is primarily due to the October 2023 reorganization and a decrease in the fair value of long-term incentive awards granted.
We had recorded a net loss of $0.2 million in 2021 for the increase in the fair market value of the derivative financial liability related to the CoC-payment. ​ Income tax ​ We recognized $1.9 million of deferred tax expense in 2023, compared to $1.5 million of deferred tax income in 2022 and $3.2 million of deferred tax expense in 2021.
In 2022, we recognized a $2.8 million net gain related to a decrease in the fair value market value of a derivative financial liability ​ Income tax ​ We recognized $2.3 million of deferred tax expense in 2024 compared to $1.9 million of deferred tax expense in 2023 and $1.5 million of deferred tax income in 2022.
We had a net loss of $308.5 million in 2023, a net loss of $126.8 million in 2022 and net income of $329.6 million in 2021. As of December 31, 2023, we had an accumulated deficit of $890.4 million (December 31, 2022: $581.9 million).
We had a net loss of $239.6 million in 2024 and a net loss of $308.5 million and $126.8 million in 2023 and 2022, respectively. As of December 31, 2024, we had an accumulated deficit of $1,130.0 million (December 31, 2023: $890.4 million).
In addition, our pledge of assets as collateral to secure our obligations under the 2023 Amended Facility may limit our ability to obtain debt financing. The 2023 Amended Facility permits us to issue up to $500.0 million of convertible debt.
In addition, our pledge of assets as collateral to secure our obligations under the 2024 Amended Facility may limit our ability to obtain debt financing.
We sublease an additional approximately 12,000 square feet of space in the Amsterdam facility, which is subject to a lease that expires in October 2028. ​ We believe that our facilities are adequate to meet current needs and that suitable alternative spaces will be available in the future on commercially reasonable terms. ​ Item 3.
We lease an additional approximately 12,000 square feet of space in the Amsterdam facility, which is subject to a lease that expires in December 2027. ​ We operate approximately 7,400 square feet of multi-use office space in Basel, Switzerland, which is subject to a lease that expires in 2026 and may be renewed for two subsequent terms of three years. ​ We believe that our facilities are adequate to meet current needs and that suitable alternative spaces will be available in the future on commercially reasonable terms. ​ Item 3.
If as of December 31, 2023 we had assumed that we would discontinue development of the TLE program, then we could have released the contingent consideration liability to income.
If as of December 31, 2024 the Company had assumed that it would discontinue development of the AMT-260 program, then the contingent consideration would have been released to income.
Other Information ​ Trading Arrangements ​ During the three months ended December 31, 2023, none of our directors or officers informed us of the adoption , modification or termination of a “ Rule 10b5-1 trading arrangement ” or “ non-Rule 10b5-1 trading arrangement ,” as each term is defined in Item 408(a) of Regulation S-K. ​ Amendments to Code of Ethics ​ On February 27, 2024, our Board approved certain amendments to our Code of Business Conduct and Ethics (as amended, the “Code”) upon the recommendation of the Audit Committee of the Board.
Other Information ​ Trading Arrangements ​ During the three months ended December 31, 2024, none of our directors or officers informed us of the adoption , modification or termination of a “ Rule 10b5-1 trading arrangement ” or “ non-Rule 10b5-1 trading arrangement ,” as each term is defined in Item 408(a) of Regulation S-K. 109 ​ Table of Contents ​
The increase in 2023 compared 2022 of $3.7 million was primarily a result of an increase in information technology expenses. Other items, net In the year ended December 31, 2023, we recognized $0.8 million in other expense in relation to a reduction in the fair market value of our equity stake in VectorY B.V. following an October 2023 financing round.
We recognized nil income related to our equity stake in VectorY B.V. in the year ended December 31, 2024. In 2023, we recognized $0.8 million in other expense related to a reduction in the fair market value of our equity stake in VectorY B.V. following an October 2023 financing round.
Our costs increased by $5.9 million in 2023 compared to 2022 as a result of incurring additional operating and depreciation expenses in both our Lexington and Amsterdam facilities.
Our costs increased by $5.9 million in 2023 compared to 2022 as a result of incurring additional operating and depreciation expenses in both our Lexington and Amsterdam facilities; ● We incurred $9.3 million in share-based compensation expenses in the year ended December 31, 2024 compared to $16.9 million in 2023 and $18.4 million in 2022.
In 2023, deferred tax expense recorded in the U.S., related to the consumption of net operating losses, more than offset the deferred tax income recorded as a result of the buildup of net operating losses by the French entity. ​ Deferred tax income recorded in 2022 results from deferred tax benefits recorded related to the buildup of net operating losses by the French entity which are partially offset by deferred tax expense recorded in the U.S. as a result of the consumption of net operating losses.
In 2024 and 2023 deferred tax expense recorded in the U.S., related to the consumption of net operating losses. ​ From 2022 up to mid-2023 we recognized deferred tax income in France as a result of the buildup of net operating losses by the French entity.
Our interest income increased in 2022 by $0.4 million compared to 2021 primarily due to the interest income earned on investment securities. ​ We recognized $41.6 million interest expense in 2023, $11.7 million in 2022 and $7.5 million in 2021.
We recognized interest income of $21.4 million in 2024, $19.6 million in 2023 and $0.6 million in 2022. Our interest income increased in 2024 by $1.9 million compared to 2023 primarily due to the interest income earned on investment securities and cash on hand.
The increase in 2023 was primarily due to an increase in the probability of making future milestone payments following the dosing of the first patient in Phase I/II clinical trial of AMT-260 after receiving IND acceptance in August 2023; ● We incurred $1.4 million of costs related to the impairment of the Lexington, MA facility right-of-use asset and related leasehold improvements for the year ended December 31, 2023 compared to nil in prior periods; and ● We incurred $6.8 million in other expenses in the year ended December 31, 2023 compared to $17.2 million in 2022 and $5.8 million in 2021.
The increase in the 2023 loss was primarily due to an increase in the probability of making future milestone payments due upon dosing of the first patient in Phase I/II clinical trial of AMT-260 after receiving IND acceptance in August 2023; and 97 ​ Table of Contents ● We incurred $9.7 million in other expenses in the year ended December 31, 2024 compared to $6.8 million in 2023 and $17.2 million in 2022.
As of December 31, 2023, our remaining commitment amounts include a EUR 30.0 million ($33.1 million) milestone payment due upon treating the first patient in a Phase I/II clinical trial for AMT-260 and EUR 160.0 million ($176.6 million) in potential milestone payments associated with Phase III development and the approvals of AMT-260 in the U.S. and European Union.
As of December 31, 2024, our remaining commitment amounts include a EUR 160.0 million ($166.2 million) in potential milestone payments associated with Phase III development and the approvals of AMT-260 in the U.S. and European Union.
The Purchaser will receive 1.85 times the upfront payment (or $693.8 million) and 1.85 times the $25.0 million milestone payment (if paid) prior to the First Hard Cap Date or, if such cap is not met, up to 2.25 times the upfront and milestone payment (if paid) through December 31, 2038.
The Purchaser will receive 1.85 times the upfront payment (or $693.8 million) until June 30, 2032 (“First Hard Cap Date”) if such thresholds are met or, if such cap is not met by June 30, 2032, up to 2.25 times of the upfront payment through December 31, 2038 (“Second Hard Cap Date”).
This was partially offset by recognizing compensation cost related to performance share units granted in 2021, for which achievement of related performance conditions was deemed probable during the year ended December 31, 2023.
This was partially offset by cost related to performance share units granted in 2021, for which achievement of related performance conditions was deemed probable in 2023 and 2024; ● We incurred $5.1 million in disposables costs in the year ended December 31, 2024 compared to $13.2 million in 2023 and $17.8 million in 2022.
The increase in 2022 compared to 2021 is primarily related to the contractual license expenses incurred in 2022. ​ ​ ​ ​ ​ ​ 94 ​ Table of Contents Selling, general and administrative expenses Our general and administrative expenses consist principally of employee, office, consulting, legal and other professional and administrative expenses.
The decrease in costs in 2023 of $10.4 million, compared to 2022, is due to decreases in contractual license expenses and consultant-related expenses. ​ Selling, general and administrative expenses Our general and administrative expenses consist principally of employee, office, consulting, legal and other professional and administrative expenses.
Other non-operating items, net Our non-operating items, net, for the years ended December 31, 2023, 2022 and 2021 were as follows: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year ended December 31, ​ ​ 2023 ​ 2022 ​ 2021 ​ 2023 vs 2022 ​ 2022 vs 2021 ​ ​ (in thousands) Interest income $ 19,562 $ 609 $ 162 $ 18,953 $ 447 Interest expense ​ ​ (41,557) ​ ​ (11,704) ​ ​ (7,474) ​ ​ (29,853) ​ ​ (4,230) Foreign currency (losses) / gains, net ​ ​ (1,691) ​ ​ 23,235 ​ ​ 29,660 ​ ​ (24,926) ​ ​ (6,425) Other non-operating gains / (losses) ​ ​ — ​ ​ 2,760 ​ ​ (160) ​ ​ (2,760) ​ ​ 2,920 Total non-operating (expense) / income, net ​ $ (23,686) ​ $ 14,900 ​ $ 22,188 ​ $ (38,586) ​ $ (7,288) ​ We recognize interest income associated with our cash and cash equivalents and investment securities.
Other non-operating items, net Our non-operating items, net, for the years ended December 31, 2024, 2023 and 2022 were as follows: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year ended December 31, ​ ​ 2024 ​ 2023 ​ 2022 ​ 2024 vs 2023 ​ 2023 vs 2022 ​ ​ (in thousands) Interest income $ 21,415 $ 19,562 $ 609 $ 1,853 $ 18,953 Interest expense - Royalty Financing Agreement ​ ​ (50,865) ​ ​ (26,933) ​ ​ — ​ ​ (23,932) ​ ​ (26,933) Interest expense - Hercules debt facility ​ ​ (12,876) ​ ​ (14,624) ​ ​ (11,704) ​ ​ 1,748 ​ ​ (2,920) Foreign currency (losses) / gains, net ​ ​ (10,507) ​ ​ (1,691) ​ ​ 23,235 ​ ​ (8,816) ​ ​ (24,926) Other non-operating gains ​ ​ — ​ ​ — ​ ​ 2,760 ​ ​ — ​ ​ (2,760) Total non-operating (expense) / income, net ​ $ (52,833) ​ $ (23,686) ​ $ 14,900 ​ $ (29,147) ​ $ (38,586) ​ We recognize interest income associated with our cash and cash equivalents and investment securities.
We recognized $2.3 million, $3.0 million and $2.4 million of collaboration revenue for the years ended December 31, 2023, 2022 and 2021, respectively. The decrease in collaboration revenue in 2023 of $0.7 million compared to 2022 was primarily related to a reduction in services requested by CSL Behring following the submissions of the BLA and MAA for HEMGENIX ®.
The decrease in collaboration revenue in 2023 of $0.7 million compared to 2022 was primarily related to a reduction in services requested by CSL Behring following the submissions of the BLA and MAA for HEMGENIX ® in 2022. ​ ​ 93 ​ Table of Contents We provided contract manufacturing service to CSL Behring between April 2022 and July 2024.
If we are unable to raise additional funds through equity or debt financings when needed, we may be required to delay, limit, reduce or terminate our product development or future commercialization efforts or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves, which could have a material adverse effect on our business, financial conditions, results of operations and cash flows. 99 ​ Table of Contents Net Cash used in / generated from operating activities ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year ended December 31, ​ 2023 2022 2021 ​ ​ ​ (in thousands) Cash flows from operating activities ​ ​ ​ ​ ​ ​ ​ ​ ​ Net (loss) / income ​ $ (308,478) ​ $ (126,789) ​ $ 329,589 Adjustments to reconcile net (loss) /income to net cash (used in) / generated from operating activities: ​ ​ ​ ​ ​ ​ ​ ​ ​ Depreciation, amortization and impairment ​ ​ 11,900 ​ ​ 8,537 ​ ​ 7,299 Amortization of premium/discount on investment securities ​ ​ (10,917) ​ ​ — ​ ​ — Share-based compensation expense ​ ​ 35,093 ​ ​ 34,204 ​ ​ 25,635 Royalty financing agreement interest expense ​ ​ 26,933 ​ ​ — ​ ​ ​ Deferred tax expense / (income) ​ ​ 1,921 ​ ​ (1,470) ​ ​ 3,210 Change in fair value of contingent consideration and derivative financial instrument, net ​ ​ 15,895 ​ ​ 4,320 ​ ​ 6,843 Unrealized foreign exchange (gains) / losses, net ​ ​ (2,206) ​ ​ (22,083) ​ ​ (31,335) Other items, net ​ ​ 4,721 ​ ​ 1,605 ​ ​ (2,800) Changes in operating assets and liabilities: ​ ​ ​ ​ ​ ​ ​ ​ ​ Accounts receivable, prepaid expenses, and other current assets and receivables ​ ​ (1,323) ​ ​ (4,083) ​ ​ (3,959) Contract asset related to CSL Behring milestone payments ​ ​ 100,000 ​ ​ (45,000) ​ ​ (55,000) Inventories ​ ​ (6,740) ​ ​ (6,924) ​ ​ - Accounts payable ​ ​ (4,169) ​ ​ 9,238 ​ ​ (727) Accrued expenses, other liabilities, and operating leases ​ ​ (6,645) ​ ​ 3,385 ​ ​ 9,204 Contingent consideration milestone payment ​ ​ (1,914) ​ ​ — ​ ​ - Net cash (used in) / generated from operating activities ​ $ (145,929) ​ $ (145,060) ​ $ 287,959 ​ Net cash used in operating activities was $145.9 million for the year ended December 31, 2023, and consisted of a net loss of $308.5 million adjusted for non-cash items, including depreciation, amortization and impairment expense of $11.9 million, amortization of the premium/discount on investment securities of $10.9 million, share-based compensation expense of $35.1 million, $26.9 million of interest expense related to the royalty financing agreement, a change in deferred taxes of $1.9 million, $15.9 million change in the fair value of contingent consideration and unrealized foreign exchange gains of $2.2 million.
Net Cash used in operating activities ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year ended December 31, ​ 2024 2023 2022 ​ ​ ​ (in thousands) Cash flows from operating activities ​ ​ ​ ​ ​ ​ ​ ​ ​ Net loss ​ $ (239,556) ​ $ (308,478) ​ $ (126,789) Adjustments to reconcile net loss to net cash used in operating activities: ​ ​ ​ ​ ​ ​ ​ ​ ​ Depreciation, amortization and impairment ​ ​ 12,641 ​ ​ 11,900 ​ ​ 8,537 Amortization of discount on investment securities ​ ​ (10,901) ​ ​ (10,917) ​ ​ — Share-based compensation expense ​ ​ 22,258 ​ ​ 35,093 ​ ​ 34,204 Royalty financing agreement interest expense, net of interest paid ​ ​ 44,203 ​ ​ 25,616 ​ ​ — Deferred tax expense / (income) ​ ​ 2,429 ​ ​ 1,921 ​ ​ (1,470) Change in fair value of contingent consideration and derivative financial instrument, net ​ ​ (1,817) ​ ​ 15,895 ​ ​ 4,320 Unrealized foreign exchange losses / (gains), net ​ ​ 15,415 ​ ​ (2,206) ​ ​ (22,083) Other items, net ​ ​ (3,848) ​ ​ 4,721 ​ ​ 1,605 Changes in operating assets and liabilities: ​ ​ ​ ​ ​ ​ ​ ​ ​ Accounts receivable, prepaid expenses, and other current assets and receivables ​ ​ (2,243) ​ ​ (1,323) ​ ​ (4,083) Contract asset related to CSL Behring milestone payments ​ ​ - ​ ​ 100,000 ​ ​ (45,000) Inventories ​ ​ 2,421 ​ ​ (6,740) ​ ​ (6,924) Accounts payable ​ ​ 1,520 ​ ​ (4,169) ​ ​ 9,238 Accrued expenses, other liabilities, and operating leases ​ ​ (5,642) ​ ​ (5,328) ​ ​ 3,385 Contingent consideration milestone payment ​ ​ (19,608) ​ ​ (1,914) ​ ​ — Net cash used in operating activities ​ $ (182,728) ​ $ (145,929) ​ $ (145,060) ​ Net cash used in operating activities was $182.7 million for the year ended December 31, 2024, and consisted of a net loss of $239.6 million adjusted for non-cash items, including depreciation, amortization and impairment expense of $12.6 million, amortization of the discount on investment securities of $10.9 million, share-based compensation expense of $22.3 million, $44.2 million of interest expense net of interest paid related to the May 2023 royalty financing agreement, a change in deferred taxes of $2.4 million, $1.8 million change in the fair value of contingent consideration and unrealized foreign exchange losses of $15.4 million.
Direct research and development expenses related to clinical development incurred in the year ended December 31, 2022 and 2021 are presented net of reimbursements due from CSL Behring.
Direct research and development expenses related to clinical development and other regulatory activities and commercialization expenses incurred in the periods ended December 31, 2023 and 2024 are presented net of reimbursements due from CSL Behring and include settlement amounts from the transition. ● Preclinical research programs .
Recently Adopted Accounting Pronouncements ​ None. ​ ​ Results of Operations ​ The following table presents a comparison of the years ended December 31, 2023, 2022 and 2021. ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year ended December 31, ​ ​ 2023 ​ 2022 ​ 2021 ​ 2023 vs 2022 ​ 2022 vs 2021 ​ ​ (in thousands) Total revenues ​ $ 15,843 ​ $ 106,483 ​ $ 524,002 ​ $ (90,640) ​ $ (417,519) Operating expenses: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Cost of revenues ​ ​ (13,628) ​ ​ (3,343) ​ ​ (24,976) ​ ​ (10,285) ​ ​ 21,633 Research and development expenses ​ ​ (214,864) ​ ​ (197,591) ​ ​ (143,548) ​ ​ (17,273) ​ ​ (54,043) Selling, general and administrative expenses ​ ​ (74,591) ​ ​ (55,059) ​ ​ (56,290) ​ ​ (19,532) ​ 1,231 Total operating expenses ​ ​ (303,083) ​ ​ (255,993) ​ ​ (224,814) ​ ​ (47,090) ​ ​ (31,179) Other income ​ ​ 6,059 ​ ​ 7,171 ​ ​ 12,306 ​ ​ (1,112) ​ ​ (5,135) Other expense ​ ​ (1,690) ​ ​ (820) ​ ​ (876) ​ ​ (870) ​ ​ 56 (Loss) / income from operations ​ ​ (282,871) ​ ​ (143,159) ​ ​ 310,618 ​ ​ (139,712) ​ ​ (453,777) Non-operating (expense) / income, net ​ ​ (23,686) ​ ​ 14,900 ​ ​ 22,188 ​ ​ (38,586) ​ ​ (7,288) (Loss) / income before income tax benefit ​ $ (306,557) ​ $ (128,259) ​ $ 332,806 ​ ​ (178,298) ​ ​ (461,065) Income tax (expense) / benefit ​ ​ (1,921) ​ ​ 1,470 ​ ​ (3,217) ​ ​ (3,391) ​ ​ 4,687 Net (loss) / income ​ $ (308,478) ​ $ (126,789) ​ $ 329,589 ​ $ (181,689) ​ $ (456,378) ​ 89 ​ Table of Contents Revenues and cost of revenues ​ Our revenues and associated costs for the years ended December 31, 2023, 2022 and 2021 were as follows: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year ended December 31, ​ 2023 2022 2021 2023 vs 2022 2022 vs 2021 ​ (in thousands) License revenues $ 2,758 ​ $ 100,000 ​ $ 517,400 ​ $ (97,242) ​ $ (417,400) Contract manufacturing revenues ​ 10,835 ​ ​ 1,717 ​ ​ — ​ ​ 9,118 ​ ​ 1,717 Collaboration revenues ​ 2,250 ​ ​ 4,766 ​ ​ 6,602 ​ ​ (2,516) ​ ​ (1,836) Total revenues $ 15,843 ​ $ 106,483 ​ $ 524,002 ​ $ (90,640) ​ $ (417,519) ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Cost of license revenues ​ (65) ​ ​ (1,254) ​ ​ (24,976) ​ ​ 1,189 ​ ​ 23,722 Cost of contract manufacturing revenues ​ (13,563) ​ ​ (2,089) ​ ​ — ​ ​ (11,474) ​ ​ (2,089) Total cost $ (13,628) ​ $ (3,343) ​ $ (24,976) ​ $ (10,285) ​ $ 21,633 ​ CSL Behring Effective on Closing of the CSL Behring Agreement we sold the exclusive global rights to the Product (“License Sale”).
We adopted ASU 2023-07 using a retrospective transition method. ​ Results of Operations ​ The following table presents a comparison of the years ended December 31, 2024, 2023 and 2022. ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year ended December 31, ​ ​ 2024 ​ 2023 ​ 2022 ​ 2024 vs 2023 ​ 2023 vs 2022 ​ ​ (in thousands) Total revenues ​ $ 27,119 ​ $ 15,843 ​ $ 106,483 ​ $ 11,276 ​ $ (90,640) Operating expenses: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Cost of license revenues ​ ​ (1,267) ​ ​ (65) ​ ​ — ​ ​ (1,202) ​ ​ (65) Cost of contract manufacturing ​ ​ (17,060) ​ ​ (13,563) ​ ​ (3,343) ​ ​ (3,497) ​ ​ (10,220) Research and development expenses ​ ​ (143,782) ​ ​ (214,864) ​ ​ (197,591) ​ ​ 71,082 ​ ​ (17,273) Selling, general and administrative expenses ​ ​ (52,657) ​ ​ (74,591) ​ ​ (55,059) ​ ​ 21,934 ​ (19,532) Total operating expenses ​ ​ (214,766) ​ ​ (303,083) ​ ​ (255,993) ​ ​ 88,317 ​ ​ (47,090) Other income ​ ​ 7,926 ​ ​ 6,059 ​ ​ 7,171 ​ ​ 1,867 ​ ​ (1,112) Other expense ​ ​ (4,573) ​ ​ (1,690) ​ ​ (820) ​ ​ (2,883) ​ ​ (870) Loss from operations ​ ​ (184,294) ​ ​ (282,871) ​ ​ (143,159) ​ ​ 98,577 ​ ​ (139,712) Non-operating expense, net ​ ​ (52,833) ​ ​ (23,686) ​ ​ 14,900 ​ ​ (29,147) ​ ​ (38,586) Loss before income tax benefit ​ $ (237,127) ​ $ (306,557) ​ $ (128,259) ​ ​ 69,430 ​ ​ (178,298) Income tax (expense) / benefit ​ ​ (2,429) ​ ​ (1,921) ​ ​ 1,470 ​ ​ (508) ​ ​ (3,391) Net loss ​ $ (239,556) ​ $ (308,478) ​ $ (126,789) ​ $ 68,922 ​ $ (181,689) ​ 92 ​ Table of Contents Revenues and cost of revenues ​ Our revenues and associated costs for the years ended December 31, 2024, 2023 and 2022 were as follows: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year ended December 31, ​ 2024 2023 2022 2024 vs 2023 2023 vs 2022 ​ (in thousands) License revenues $ 10,133 ​ $ 2,758 ​ $ 100,000 ​ $ 7,375 ​ $ (97,242) Contract manufacturing revenues ​ 6,114 ​ ​ 10,835 ​ ​ 1,717 ​ ​ (4,721) ​ ​ 9,118 Collaboration revenues ​ 10,872 ​ ​ 2,250 ​ ​ 4,766 ​ ​ 8,622 ​ ​ (2,516) Total revenues $ 27,119 ​ $ 15,843 ​ $ 106,483 ​ $ 11,276 ​ $ (90,640) ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Cost of license revenues ​ (1,267) ​ ​ (65) ​ ​ (1,254) ​ ​ (1,202) ​ ​ 1,189 Cost of contract manufacturing revenues ​ (17,060) ​ ​ (13,563) ​ ​ (2,089) ​ ​ (3,497) ​ ​ (11,474) Total cost $ (18,327) ​ $ (13,628) ​ $ (3,343) ​ $ (4,699) ​ $ (10,285) ​ CSL Behring We sold the exclusive global rights to HEMGENIX® to CSL Behring in 2021 (“License Sale”).
In 2023, we recognized $5.0 million in income related to payments received from European authorities to subsidize our research and development efforts in the Netherlands compared to $5.6 million in 2022 and $5.3 million in 2021. 95 ​ Table of Contents Other income for the years ended December 31, 2023, 2022, and 2021 also includes income from the subleasing of a portion of our Amsterdam facility.
We recognized other income of $0.3 million related to the equity stake in 2022. In 2024, we recognized $5.6 million in income related to payments received from European authorities to subsidize our research and development efforts in the Netherlands and France compared to $5.3 million in 2023 and $6.1 million in 2022.
Our interest expense in 2022 primarily increased by $4.2 million compared to 2021 due to an increase in market interest rates in 2022. We hold monetary items and enter into transactions in foreign currencies, predominantly in euros and U.S. dollars. We recognize foreign exchange results related to changes in these foreign currencies.
We hold monetary items and enter into transactions in foreign currencies, predominantly in euros and U.S. dollars. We recognize foreign exchange results related to changes in these foreign currencies.
In September 2023, following the FDA’s clearance of the IND application for AMT-260, we made a payment of $10.6 million to the former shareholders of uniQure France SAS based on contractually defined milestones. $9.6 million of this payment related to a contingent consideration of which $7.6 million was classified as cash flows from financing activities and $1.9 million was classified as a net cash flow used in operating activities.
In September 2023, following the FDA’s clearance of the IND application for AMT-260, we made a payment of EUR 10.0 million ($10.7 million) to the former shareholders of uniQure France SAS based on contractually defined milestones.
This also resulted in an increase of the probability that AMT-260 may advance to late-stage development and commercialization. The fair value of the contingent consideration liability as of December 31, 2023 was $43.0 million and as of December 31, 2022 was $35.3 million.
The increase in probabilities resulted in a $14.2 million expense in the year ended December 31, 2023 and a $4.4 million expense in the year ended December 31, 2022. This also resulted in an increase of the probability that AMT-260 may advance to late-stage development and commercialization.
A change in the outcome of any of these variables with respect to our product candidates that we may develop could mean a significant change in the expenses and timing associated with the development of such product candidate.
A change in the outcome of any of these variables with respect to our product candidates that we may develop could mean a significant change in the expenses and timing associated with the development of such product candidate. ​ 95 ​ Table of Contents Research and development expenses for the year ended December 31, 2024 were $143.8 million, compared to $214.9 million and $197.6 million for the years ended December 31, 2023 and 2022, respectively.

… 203 more changes not shown on this page.

Other QURE 10-K year-over-year comparisons