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What changed in AMICUS THERAPEUTICS, INC.'s 10-K — 2024 vs 2025

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Paragraph-level year-over-year comparison of AMICUS THERAPEUTICS, INC.'s 2024 and 2025 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 2025 report.

+358 added−297 removedSource: 10-K (2026-02-20) vs 10-K (2025-02-19)

Top changes in AMICUS THERAPEUTICS, INC.'s 2025 10-K

358 paragraphs added · 297 removed · 248 edited across 8 sections

Item 1. Business

Business — how the company describes what it does

74 edited+49 added−11 removed184 unchanged
Biggest changeThe following table lists our principal competitors and publicly available information on the status of their clinical-stage product offerings: -11- Table of Contents Competitor (1) Indication Product Class of Product Status 2024 Sales (in millions) Sanofi Fabry Disease Fabrazyme ® ERT Marketed €1,047 Pompe Disease Myozyme ® / Lumizyme ® ERT Marketed €671 Pompe Disease Nexviazyme ® / Nexviadyme ® ERT Marketed €667 Fabry Disease Venglustat Oral glucosylceramide synthase ("GCS") Inhibitor Phase 3 N/A Takeda (2) Fabry Disease Replagal ® ERT Marketed ¥78,700 Chiesi (3) Fabry Disease ELFABRIO ® ERT Marketed $14.0 Eleva Fabry Disease RPV-001 ERT Phase 1/2 N/A Idorsia Fabry Disease Lucerastat Oral GCS Inhibitor Phase 3 N/A AceLink Fabry Disease AL1211 Oral GCS Inhibitor Phase 1/2 N/A Sangamo Fabry Disease Isaralgagene civaparvovec Gene Therapy Phase 1/2 N/A UniQure Fabry Disease AMT-191 Gene Therapy Phase 1/2 N/A 4DMT Fabry Disease 4D-310 Gene Therapy Phase 1/2 N/A Bayer Pompe Disease ACTUS-101 Gene Therapy Phase 1/2 N/A Astellas Pompe Disease AT845 Gene Therapy Phase 1/2 N/A Roche Pompe Disease SPK-3006 Gene Therapy Phase 1/2 N/A GeneCradle Pompe Disease GC301 Gene Therapy Phase 1/2 N/A Aro Pompe Disease ABX1100 Gene Therapy Phase 1/2 N/A Maze Pompe Disease MZE001 Oral glycogen synthase ("GYS1") Inhibitor Phase 1/2 N/A _____________________________ (1) Reflects commercial products and product candidates for which IND has been filed or are in clinical development.
Biggest changeThe following table lists our principal competitors and publicly available information on the status of their clinical-stage product offerings: -12- Table of Contents Competitor (1)(2) Indication Product Class of Product Status Sanofi Fabry Disease Fabrazyme ® ERT Marketed Pompe Disease Myozyme ® / Lumizyme ® ERT Marketed Pompe Disease Nexviazyme ® / Nexviadyme ® ERT Marketed Fabry Disease Venglustat Oral glucosylceramide synthase ("GCS") Inhibitor Phase 3 Takeda Fabry Disease Replagal ® ERT Marketed Chiesi Fabry Disease ELFABRIO ® ERT Marketed Idorsia Fabry Disease Lucerastat Oral GCS Inhibitor Phase 3 Sangamo Fabry Disease Isaralgagene civaparvovec Gene Therapy Pivotal Bayer Pompe Disease ACTUS-101 Gene Therapy Phase 1/2 Maze/Shionogi Pompe Disease MZE001 Oral glycogen synthase ("GYS1") Inhibitor Phase 1/2 Travere FSGS Sparsentan ERA Inhibitor Phase 3 Vertex FSGS VX-147 Oral Inhibitor Phase 3 _____________________________ (1) Reflects commercial products and product candidates for which Investigational New Drug application ("IND") has been filed or are in clinical development.
A person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation; • the U.S. civil False Claims Act (which can be enforced through “qui tam,” or whistleblower actions, by private citizens on behalf of the federal government), prohibits any person from, among other things, knowingly presenting, or causing to be presented false or fraudulent claims for payment of government funds or knowingly making, using or causing to be made or used, a false record or statement material to an obligation to pay money to the government or knowingly and improperly avoiding, decreasing or concealing an obligation to pay money to the U.S. federal government; -18- Table of Contents • U.S. federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, which imposes criminal liability and amends provisions on the reporting, investigation, enforcement, and penalizing of civil liability for, among other things, knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program, or knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false statement, in connection with the delivery of or payment for healthcare benefits, items or services by a healthcare benefit program, which includes both government and privately funded benefits programs; similar to the U.S. federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation; • state laws and regulations, including state anti-kickback and false claims laws, that may apply to our business practices, including but not limited to, research, distribution, sales and marketing arrangements and claims involving healthcare items or services reimbursed by any third-party payer, including private insurers; state laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the U.S. federal government, or otherwise restrict payments that may be made to healthcare providers and other potential referral sources; and state laws and regulations that require drug manufacturers to file reports relating to pricing and marketing information, which requires tracking gifts and other remuneration and items of value provided to healthcare professionals and entities; and • the Physician Payments Sunshine Act, implemented as the Open Payments program, and its implementing regulations, requires certain manufacturers of drugs, devices, biologics and medical supplies that are reimbursable under Medicare, Medicaid, or the Children’s Health Insurance Program to report annually to CMS information related to certain payments made in the preceding calendar year and other transfers of value to physicians and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members; beginning in 2022, applicable manufacturers are required to report such information regarding payments and transfers of value provided, as well as ownership and investment interests held, during the previous year to physician assistants, nurse practitioners, clinical nurse specialists, certified nurse anesthetists, and certified nurse-midwives.
A person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation; • the U.S. civil False Claims Act (which can be enforced through “qui tam,” or whistleblower actions, by private citizens on behalf of the federal government), prohibits any person from, among other things, knowingly presenting, or causing to be presented false or fraudulent claims for payment of government funds or knowingly making, using or causing to be made or used, a false record or statement material to an obligation to pay money to the government or knowingly and improperly avoiding, decreasing or concealing an obligation to pay money to the U.S. federal government; • U.S. federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, which imposes criminal liability and amends provisions on the reporting, investigation, enforcement, and penalizing of civil liability for, among other things, knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program, or knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false statement, in connection with the delivery of or payment for healthcare benefits, items or services by a healthcare benefit program, which includes both government and privately funded benefits programs; similar to the U.S. federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation; • state laws and regulations, including state anti-kickback and false claims laws, that may apply to our business practices, including but not limited to, research, distribution, sales and marketing arrangements and claims involving healthcare items or services reimbursed by any third-party payer, including private insurers; state laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the U.S. federal government, or otherwise restrict payments that may be made to healthcare providers and other potential referral sources; and state laws and regulations that require drug manufacturers to file reports relating to pricing and marketing information, which requires tracking gifts and other remuneration and items of value provided to healthcare professionals and entities; and • the Physician Payments Sunshine Act, implemented as the Open Payments program, and its implementing regulations, requires certain manufacturers of drugs, devices, biologics and medical supplies that are reimbursable under Medicare, Medicaid, or the Children’s Health Insurance Program to report annually to CMS information related to certain payments made in the preceding calendar year and other transfers of value to physicians and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members; beginning in 2022, applicable manufacturers are required to report such information regarding payments and transfers of value provided, as well as ownership and investment interests held, during the previous year to physician assistants, nurse practitioners, clinical nurse specialists, certified nurse anesthetists, and certified nurse-midwives.
This rolling review is available if the applicant provides, and the FDA approves, a schedule for the submission of the remaining information and the applicant pays applicable user fees. However, the FDA's review period as specified under PDUFA V for filing and reviewing an application does not begin until the last section of the NDA or BLA has been submitted.
This rolling review is available if the applicant provides, and the FDA approves, a schedule for the submission of the remaining information and the applicant pays applicable user fees. However, the FDA's review period as specified under PDUFA for filing and reviewing an application does not begin until the last section of the NDA or BLA has been submitted.
Priority Review Under FDA policies, a drug candidate is eligible for priority review, or review within six months from filing for a new molecular entity ("NME") or six months from submission for a non-NME if the drug candidate provides a significant improvement compared to marketed drugs in the treatment, diagnosis, or prevention of a disease, rather than the standard review of ten months under current PDUFA V guidelines.
Priority Review Under FDA policies, a drug candidate is eligible for priority review, or review within six months from filing for a new molecular entity ("NME") or six months from submission for a non-NME if the drug candidate provides a significant improvement compared to marketed drugs in the treatment, diagnosis, or prevention of a disease, rather than the standard review of ten months under current PDUFA guidelines.
In accordance with the license agreement, a consent judgment and permanent injunction was entered with the Court and all Hatch-Waxman litigation between Amicus and Teva has been terminated. As required by law, Amicus and Teva have submitted the confidential license agreement to the U.S. Federal Trade Commission and the U.S.
In accordance with the license agreement, a consent judgment and permanent injunction was entered with the District Court and all Hatch-Waxman litigation between Amicus and Teva has been terminated. As required by law, Amicus and Teva have submitted the confidential license agreement to the U.S. Federal Trade Commission and the U.S.
Most such applications for standard review are reviewed within 12 months under the Prescription Drug User Fee Act ("PDUFA V") (two months for filing plus ten months for review). The FDA attempts to review a drug candidate that is eligible for priority review within six months, as discussed below.
Most such applications for standard review are reviewed within 12 months under the Prescription Drug User Fee Act ("PDUFA") (two months for filing plus ten months for review). The FDA attempts to review a drug candidate that is eligible for priority review within six months, as discussed below.
Further changes to and under the Affordable Care Act remain possible but it is unknown what form any such changes or any law proposed to replace or revise the Affordable Care Act would take, and how or whether it may affect our business in the future.
Changes to and under the Affordable Care Act remain possible but it is unknown what form any such changes or any law proposed to replace or revise the Affordable Care Act would take, and how or whether it may affect our business in the future.
Additionally, the Fast Track designation may be withdrawn by the FDA if the FDA believes that the designation is no longer supported by data emerging in the clinical trial process. -16- Table of Contents Breakthrough Therapy Designation Breakthrough Therapy designation is intended to expedite the development and review of a candidate that is planned for use to treat a serious or life-threatening disease or condition when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints.
Additionally, the Fast Track designation may be withdrawn by the FDA if the FDA believes that the designation is no longer supported by data emerging in the clinical trial process. -17- Table of Contents Breakthrough Therapy Designation Breakthrough Therapy designation is intended to expedite the development and review of a candidate that is planned for use to treat a serious or life-threatening disease or condition when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints.
These laws include: • the U.S. federal Anti-Kickback Statute, which prohibits, among other things, persons or entities from knowingly and willfully soliciting, offering, receiving or paying any remuneration, directly or indirectly, overtly or covertly, in cash or in kind, to induce or reward either the referral of an individual for, or the purchase, lease, order, or arranging for or recommending the purchase, lease or order of, any good or service, for which payment may be made, in whole or in part, under federal healthcare programs such as Medicare and Medicaid.
These laws include: -19- Table of Contents • the U.S. federal Anti-Kickback Statute, which prohibits, among other things, persons or entities from knowingly and willfully soliciting, offering, receiving or paying any remuneration, directly or indirectly, overtly or covertly, in cash or in kind, to induce or reward either the referral of an individual for, or the purchase, lease, order, or arranging for or recommending the purchase, lease or order of, any good or service, for which payment may be made, in whole or in part, under federal healthcare programs such as Medicare and Medicaid.
New efficacy claims require submission and approval of an NDA supplement and BLA supplement for each new indication. -15- Table of Contents The efficacy claims typically require new clinical data similar to those included in the original application. The FDA uses the same procedures and actions in reviewing NDA and BLA supplements as it does in reviewing NDAs and BLAs.
New efficacy claims require submission and approval of an NDA supplement and BLA supplement for each new indication. -16- Table of Contents The efficacy claims typically require new clinical data similar to those included in the original application. The FDA uses the same procedures and actions in reviewing NDA and BLA supplements as it does in reviewing NDAs and BLAs.
The approval process varies from country to country, and the time may be longer or shorter than that required for FDA approval. -19- Table of Contents To obtain regulatory approval of an orphan drug under the E.U. regulatory system, we are mandated to submit a marketing authorization application ("MAA") to be assessed in the centralized procedure.
The approval process varies from country to country, and the time may be longer or shorter than that required for FDA approval. To obtain regulatory approval of an orphan drug under the E.U. regulatory system, we are mandated to submit a marketing authorization application ("MAA") to be assessed in the centralized procedure.
In addition, the PDMA sets forth civil and criminal penalties for violations. Regulation Outside the U.S. In addition to regulations in the U.S., we are subject to a variety of regulations in other jurisdictions governing clinical studies, commercial sales, and distribution of our products.
In addition, the PDMA sets forth civil and criminal penalties for violations. -20- Table of Contents Regulation Outside the U.S. In addition to regulations in the U.S., we are subject to a variety of regulations in other jurisdictions governing clinical studies, commercial sales, and distribution of our products.
Pombiliti ® + Opfolda ® (also referred to as "cipaglucosidase alfa-atga/miglustat") is approved in the U.S., the E.U., the U.K., and Switzerland. Multiple regulatory submissions and reimbursement processes with global health authorities are currently underway.
Pombiliti ® + Opfolda ® (also referred to as "cipaglucosidase alfa-atga/miglustat") is approved in the U.S., the E.U., the U.K., Canada, Australia, Switzerland, and Japan. Multiple regulatory submissions and reimbursement processes with global health authorities are currently underway.
Patent term extensions and adjustments, supplementary protection certificates, and pediatric exclusivity periods are not reflected in the expiration dates listed above and may extend protection. -8- Table of Contents In addition to our clinical programs, we actively monitor and file patent applications in the U.S. and in foreign countries on relevant technologies and pre-clinical programs.
Patent term extensions and adjustments, supplementary protection certificates, and pediatric exclusivity periods are not reflected in the expiration dates listed above and may extend protection. In addition to our clinical programs, we actively monitor and file patent applications in the U.S. and in foreign countries on relevant technologies and pre-clinical programs.
The conduct of the preclinical tests must comply with federal regulations and requirements including GLP. The results of preclinical testing are submitted to the FDA as part of an IND along with other information including information about product chemistry, manufacturing and controls, and at least one proposed clinical trial protocol.
The conduct of the preclinical tests must comply with federal regulations and requirements including Good Laboratory Practices ("GLP"). The results of preclinical testing are submitted to the FDA as part of an IND along with other information including information about product chemistry, manufacturing and controls ("CMC"), and at least one proposed clinical trial protocol.
Supporting our global employees is an essential part of the core values and culture at Amicus. Tied to these values and culture, we believe our success and our ability to help patients depends on our capability to attract, develop and retain key personnel. As of December 31, 2024, we had 499 full-time employees.
Supporting our global employees is an essential part of the core values and culture at Amicus. Tied to these values and culture, we believe our success and our ability to help patients depends on our capability to attract, develop and retain key personnel. As of December 31, 2025, we had 511 full-time employees.
Any waivers or material amendments to the Code will be posted promptly on our website. -24- Table of Contents
Any waivers or material amendments to the Code will be posted promptly on our website. -25- Table of Contents
As of December 31, 2024, 58% of our global workforce, 42% of our executive management team and 33% of our Board of Directors were women. Our Mission to ‘Always Put Patients First’ helps keep our employees engaged with this sense of purpose.
As of December 31, 2025, 58% of our global workforce, 27% of our executive management team and 33% of our Board of Directors were women. Our Mission to ‘Always Put Patients First’ helps keep our employees engaged with this sense of purpose.
In the fourth quarter of 2022, we received Paragraph IV Certification Notice Letters from Teva Pharmaceuticals USA, Inc. ("Teva"), Aurobindo Pharma Limited ("Aurobindo"), and Lupin Limited ("Lupin") in connection with Abbreviated New Drug Applications (“ANDA”) filed with the FDA requesting approval to market generic Galafold ® .
In the fourth quarter of 2022, we received Paragraph IV Certification Notice Letters from Teva Pharmaceuticals Inc. ("Teva"), Aurobindo Pharma Limited ("Aurobindo"), and Lupin Ltd. ("Lupin") in connection with Abbreviated New Drug Applications (“ANDA”) filed with the FDA requesting approval to market generic Galafold ® . We filed lawsuits against Teva, Lupin, and Aurobindo in the U.S.
Long-term preclinical safety evaluations, such as animal tests of reproductive toxicity and carcinogenicity, continue during the IND phase of development. Reproductive toxicity studies are required to allow inclusion of women of childbearing potential in clinical trials, whereas carcinogenicity studies are required for registration. The results of these long-term studies would eventually be described in product labeling.
Long-term preclinical safety evaluations, such as animal tests of reproductive toxicity and carcinogenicity, continue during the IND phase of development. Reproductive toxicity studies are required to allow inclusion of women of childbearing potential in clinical trials, whereas carcinogenicity studies are required for registration.
For the year ended December 31, 2024, Galafold ® revenue was $458.1 million of consolidated revenue, which represented an increase of $70.3 million compared to the prior year. We continue to see strong commercial momentum and expansion into additional geographies. • Commercial and regulatory success in Pompe disease .
We continue to see strong commercial momentum and expansion into additional geographies. • Commercial and regulatory success in Pompe disease . For the year ended December 31, 2025, Pombiliti ® + Opfolda ® revenue was $112.5 million of consolidated revenue, which represented an increase of $42.3 million compared to the prior year.
Any patents issuing from these applications will expire between 2036 and 2043. We anticipate listing these patents in the FDA Orange Book if issued. • We own several issued U.S. patents that cover various aspects of Opfolda ® and Pombiliti ® , a pharmacological chaperon/ERT combination in the treatment of Pompe disease, which expire between 2033 and 2037.
We anticipate listing these patents in the FDA Orange Book if issued. -8- Table of Contents • We own several issued U.S. patents that cover various aspects of Opfolda ® and Pombiliti ® , a pharmacological chaperon/ERT combination in the treatment of Pompe disease, which expire between 2033 and 2038.
Total cash, cash equivalents, and marketable securities as of December 31, 2024 was $249.9 million. -5- Table of Contents Our Commercial Products and Product Candidates Galafold ® (migalastat HCl) for Fabry Disease Our oral precision medicine Galafold ® was granted accelerated approval by the FDA in August 2018 for the treatment of adults with a confirmed diagnosis of Fabry disease and an amenable galactosidase alpha gene ("GLA") variant based on in vitro assay data.
Our Commercial Products and Product Candidates Galafold ® (migalastat HCl) for Fabry Disease Our oral precision medicine Galafold ® was granted accelerated approval by the FDA in August 2018 for the treatment of adults with a confirmed diagnosis of Fabry disease and an amenable galactosidase alpha gene ("GLA") variant based on in vitro assay data.
The NDA or BLA must include the results of all preclinical, clinical, and other testing and a compilation of data relating to the product's pharmacology, chemistry, manufacture, and controls. The cost of preparing and submitting an NDA or BLA is substantial.
FDA approval of the NDA or BLA is required before marketing of the product may begin in the U.S. The NDA or BLA must include the results of all preclinical, clinical, and other testing and a compilation of data relating to the product's pharmacology, chemistry, manufacture, and controls. The cost of preparing and submitting an NDA or BLA is substantial.
We are exploring potential collaborations, alliances, and various other business development opportunities on a regular basis. These opportunities may include business combinations, partnerships, the strategic out-licensing of certain assets, or the acquisition of preclinical-stage, clinical-stage, or marketed products or novel technologies consistent with our corporate strategy to develop and provide therapies to patients living with rare and orphan diseases.
These opportunities may include business combinations, partnerships, the strategic in-licensing or out-licensing of certain assets, or the acquisition of preclinical-stage, clinical-stage, or marketed products or novel technologies consistent with our corporate strategy to develop and provide therapies to patients living with rare and orphan diseases.
As an orally administered monotherapy, Galafold ® is designed to bind to and stabilize an endogenous alpha-galactosidase A ("alpha-Gal A") enzyme in those patients with genetic variants identified as amenable in a Good Laboratory Practice ("GLP") cell-based amenability assay. Next-Generation for Fabry Disease We are committed to continued innovation for all people living with Fabry disease.
As an orally administered monotherapy, Galafold ® is designed to bind to and stabilize an endogenous alpha-galactosidase A ("alpha-Gal A") enzyme in those patients with genetic variants identified as amenable in a Good Laboratory Practice ("GLP") cell-based amenability assay.
The FDA has issued various guidance documents regarding gene therapies, which outline additional factors that the FDA will consider at each of the above stages of development and relate to, among other things: the proper preclinical assessment of gene therapies; the CMC information that should be included in an IND application; the proper design of tests to measure product potency in support of an IND or BLA application; and measures to observe delayed adverse effects in subjects who have been exposed to investigational gene therapies when the risk of such effects is high.
The FDA has issued various guidance documents regarding gene therapies, which outline additional factors that the FDA will consider at each of the above stages of development and relate to, among other things: the proper preclinical assessment of gene therapies; the use of innovative clinical trial designs to expedite development, including single-arm trials utilizing participants as their own controls and externally controlled studies utilizing historical or real-world data as the comparator group; the CMC information that should be included in an IND application; the proper design of tests to measure product potency in support of an IND or BLA application; and measures to observe delayed adverse effects in subjects who have been exposed to investigational gene therapies when the risk of such effects is high.
The IRA could have the effect of reducing the prices we can charge and reimbursement we receive for our products, if approved, thereby reducing our profitability, and could have a material adverse effect on our financial condition, results of operations, and growth prospects.
The IRA could have the effect of reducing the prices we can charge and reimbursement we receive for future products or product candidates, if approved, thereby reducing our profitability, and could have a material adverse effect on our financial condition, results of operations, and growth prospects. The full impact of the IRA on the pharmaceutical industry in general remains uncertain.
The criteria are essentially the same, but have been tailored for the GB market, e.g. the prevalence of the condition in GB (rather than the E.U.) must not be more than 5 in 10,000.
Instead, the MHRA reviews applications for orphan designation in parallel to the corresponding MA application. The criteria are essentially the same, but have been tailored for the GB market, e.g. the prevalence of the condition in GB (rather than the E.U.) must not be more than 5 in 10,000.
The new guidance has been given effect via the Human Medicines Regulations ("Amendment etc.") ("E.U. Exit") Regulations 2019 (the "Exit Regulations"). The U.K. regulatory regime largely mirrors that of the E.U.
The new guidance has been given effect via the Human Medicines Regulations ("Amendment etc.") ("E.U. Exit") Regulations 2019 (the "Exit Regulations").
As such, the scheduled Markman hearing was deemed unneeded and cancelled. In October 2024, the Company entered into a non-exclusive, non-transferable, royalty-free, fully paid-up license with Teva which will allow Teva to market its generic version of Galafold ® in the United States beginning on January 30, 2037, or earlier in certain circumstances.
In October 2024, we entered into a non-exclusive, non-transferable, royalty-free license with Teva which will allow Teva to market its generic version of Galafold ® in the United States beginning on January 30, 2037, or earlier in certain circumstances.
Complexities associated with the larger, and often more complex, structures of biological products, as well as the process by which such products are manufactured, pose significant hurdles to implementation that are still being evaluated by the FDA. Under the BPCIA, a reference biologic is granted 12 years of exclusivity from the time of first licensure of the reference product.
Complexities associated with the larger, and often more complex, structures of biological products, as well as the process by which such products are manufactured, pose significant hurdles to implementation that are still being evaluated by the FDA.
Pompe disease is a rare genetic disease with a traditionally used incidence rate of 1:40,000 (European Journal of Human Genetics 1999). However, it’s increasingly recognized that the incidence rate varies among different ethnic groups, forms of the disease (infantile onset vs late onset Pompe Disease) and countries (Molecular Genetics and Metabolism Reports 2021).
However, it’s increasingly recognized that the incidence rate varies among different ethnic groups, forms of the disease (infantile onset vs late onset Pompe Disease) and countries (Molecular Genetics and Metabolism Reports 2021).
We have implemented appropriate controls for assuring the quality of both active biopharmaceutical ingredients and final drug products. Product specifications will be established in concurrence with regulatory bodies at the time of product registration. Our current arrangement with third-party manufacturers provide sufficient quantities of our program materials to meet anticipated clinical and commercial demands.
We have implemented appropriate controls for assuring the quality of both active biopharmaceutical ingredients and final drug products. Product specifications will be established in concurrence with regulatory bodies at the time of product registration.
We have obtained orphan drug designation in Japan for migalastat for the treatment of Fabry Disease. We also have other Orphan Drug applications approved in other world markets including Switzerland, Australia, South Korea and Taiwan.
We also have other Orphan Drug applications approved in other world markets including Switzerland, Australia, South Korea and Taiwan.
The address of our global headquarters is 47 Hulfish Street, Princeton, NJ 08542 and our telephone number is 609-662-2000. Our website address is www.amicusrx.com .
Our Corporate Information We were incorporated under the laws of the State of Delaware on February 4, 2002. The address of our global headquarters is 47 Hulfish Street, Princeton, NJ 08542 and our telephone number is 609-662-2000. Our website address is www.amicusrx.com .
Our ability to maintain and solidify our proprietary position for our technology will depend on our success in promptly filing patent applications on new discoveries, and in obtaining effective claims and enforcing those claims once granted.
The patent positions of companies like ours are generally uncertain and involve complex legal, technical, scientific, and factual questions. Our ability to maintain and solidify our proprietary position for our technology will depend on our success in promptly filing patent applications on new discoveries, and in obtaining effective claims and enforcing those claims once granted.
The FDA has established the Office of Tissue and Advanced Therapies within the Center for Biologics Evaluation and Research, or CBER, to consolidate the review of gene therapy and related products, and has established the Cellular, Tissue and Gene Therapies Advisory Committee to advise CBER in its review. -13- Table of Contents In addition to the regulations discussed above, there are a number of additional standards that apply to clinical trials involving gene therapies.
The FDA has established the Office of Tissue and Advanced Therapies within the Center for Biologics Evaluation and Research, or CBER, to consolidate the review of gene therapy and related products, and has established the Cellular, Tissue and Gene Therapies Advisory Committee to advise CBER in its review.
Collaboration and License Agreements We have acquired rights to develop and commercialize our product candidates through licenses granted by various parties. We have certain obligations under these acquisitions or licensing agreements, including diligence obligations and payments, which are contingent upon achieving various development, regulatory and commercial milestones.
We have certain obligations under these acquisitions or licensing agreements, including diligence obligations and payments, which are contingent upon achieving various development, regulatory and commercial milestones.
Competition Overview The biotechnology and pharmaceutical industries are characterized by rapidly advancing technologies, intense competition, and a strong emphasis on proprietary products. In addition, several large pharmaceutical companies are increasingly focused on developing therapies for the treatment of rare diseases through organic growth, acquisitions, and partnerships.
In addition, several large pharmaceutical companies are increasingly focused on developing therapies for the treatment of rare diseases through organic growth, acquisitions, and partnerships.
Under the terms of the Collaboration Agreement, GSK is eligible to receive post-approval and sales-based milestones up to $40 million, as well as tiered royalties in the mid-teens in eight major markets outside the U.S. -10- Table of Contents Manufacturing We continue to rely on contract manufacturers to supply the active biopharmaceutical ingredients and finished goods for our products and product candidates.
Under the terms of the Collaboration Agreement, GSK is eligible to receive post-approval and sales-based milestones up to $40 million, as well as tiered royalties in the mid-teens in eight major markets outside the U.S.
The review process may be extended by the FDA for three additional months to evaluate major amendments submitted during the pre-specified PDUFA V review clock.
The review process may be extended by the FDA for three additional months to evaluate major amendments submitted during the pre-specified PDUFA review clock. Also, delays may occur due to changing policies, shifting priorities, and recent staffing cuts at the FDA.
Orphan drug designation is only available if there is no other satisfactory method approved in the E.U. of diagnosing, preventing, or treating the condition, or if such a method exists, the proposed orphan drug will be of significant benefit to patients. -20- Table of Contents Orphan drug designation provides opportunities for fee reductions, protocol assistance and access to the centralized procedure before and during the first year after marketing approval.
Orphan drug designation is only available if there is no other satisfactory method approved in the E.U. of diagnosing, preventing, or treating the condition, or if such a method exists, the proposed orphan drug will be of significant benefit to patients.
The effects of the IRA on our business and the pharmaceutical industry in general is not yet known. Human Capital At Amicus, one of our founding principles is that we believe in each other to foster teamwork and respect for each individuals' contribution. Our passion for making a difference unites us.
Additional reform measures may be adopted in the future. -24- Table of Contents Human Capital At Amicus, one of our founding principles is that we believe in each other to foster teamwork and respect for each individuals' contribution. Our passion for making a difference unites us.
As part of our long-term commitment, we are also continuing discovery for next-generation genetic medicines. Fabry Disease Background Patients with Fabry disease have an inherited deficiency of the alpha-Gal A enzyme that would normally degrade the lipid substrate globotriaosylceramide in the lysosome.
Fabry Disease Background Patients with Fabry disease have an inherited deficiency of the alpha-Gal A enzyme that would normally degrade the lipid substrate globotriaosylceramide in the lysosome.
Pompe disease ranges from a rapidly fatal infantile form with severe cardiac involvement to a more slowly progressive, late-onset form primarily affecting skeletal muscle. All forms are characterized by severe muscle weakness that worsens over time. In the early-onset form, patients are usually diagnosed shortly after birth and often experience enlargement of the heart and severe muscle weakness.
GAA deficiency causes accumulation of glycogen in cells, which is believed to result in the clinical manifestations of Pompe disease. Pompe disease ranges from a rapidly fatal infantile form with severe cardiac involvement to a more slowly progressive, late-onset form primarily affecting skeletal muscle. All forms are characterized by severe muscle weakness that worsens over time.
Failure to comply with applicable U.S. requirements may subject a company to a variety of administrative or judicial sanctions, such as FDA refusal to file a marketing application, to issue complete response letters or to not approve pending NDAs or Biologics License Applications ("BLAs"), or to issue warning letters, untitled letters, Form 483s, product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, civil penalties, litigation, government investigation, and criminal prosecution. -12- Table of Contents Biopharmaceutical product development in the U.S. typically involves nonclinical laboratory and animal tests, the submission to the FDA of an Investigational New Drug application ("IND"), which must become effective before clinical testing may commence, and adequate and well-controlled clinical trials to establish the safety and effectiveness of the drug for each indication for which FDA approval is sought.
Failure to comply with applicable U.S. requirements may subject a company to a variety of administrative or judicial sanctions, such as FDA refusal to file a marketing application, to issue complete response letters or to not approve pending NDAs or Biologics License Applications ("BLAs"), or to issue warning letters, untitled letters, Form 483s, product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, civil penalties, litigation, government investigation, and criminal prosecution.
United States Healthcare Reform The United States and many foreign jurisdictions have enacted or proposed legislative and regulatory changes affecting the healthcare system, including implementing cost-containment programs to limit the growth of government-paid healthcare costs, including price controls, restrictions on reimbursement and requirements for substitution of generic products for branded prescription drugs. -22- Table of Contents In the United States, the Patient Protection and Affordable Care Act, as amended by the Health Care and Education Affordability Reconciliation Act, or collectively the Affordable Care Act, was intended to broaden access to health insurance, reduce or constrain the growth of healthcare spending, enhance remedies against fraud and abuse, add transparency requirements for the healthcare and health insurance industries, impose new taxes and fees on the health industry and impose additional health policy reforms.
In the United States, the Patient Protection and Affordable Care Act, as amended by the Health Care and Education Affordability Reconciliation Act, or collectively the Affordable Care Act, was intended to broaden access to health insurance, reduce or constrain the growth of healthcare spending, enhance remedies against fraud and abuse, add transparency requirements for the healthcare and health insurance industries, impose new taxes and fees on the health industry and impose additional health policy reforms.
The FDA may then approve the new product candidate for all or some of the label indications for which the referenced product has been approved, as well as for any new indication sought by the Section 505(b)(2) applicant. -17- Table of Contents To the extent that the Section 505(b)(2) applicant is relying on studies conducted for an already-approved product, the applicant is required to certify to the FDA concerning any patents listed for the approved product in the Orange Book to the same extent as an ANDA applicant.
To the extent that the Section 505(b)(2) applicant is relying on studies conducted for an already-approved product, the applicant is required to certify to the FDA concerning any patents listed for the approved product in the Orange Book to the same extent as an ANDA applicant.
In the fourth quarter of 2023, a stipulation order to stay litigation with respect to Lupin was ordered. Additionally, in the first quarter of 2024, a stipulation was filed with the court and approved by the presiding judge, whereby the parties agreed to accept our definition of the terms that were in dispute.
Additionally, in the first quarter of 2024, a stipulation was filed with the court and approved by the presiding judge, whereby the parties agreed to accept our definition of a term that was in dispute. As such, the scheduled Markman hearing was deemed unneeded and cancelled.
Fee reductions are not limited to the first year after marketing approval for small and medium enterprises.
Orphan drug designation provides opportunities for fee reductions, protocol assistance and access to the centralized procedure before and during the first year after marketing approval. Fee reductions are not limited to the first year after marketing approval for small and medium enterprises.
If a member state cannot approve the assessment report and related materials on the grounds of potential serious risk to the public health, the disputed points may eventually be referred to the European Commission, whose decision is binding on all member states.
If a member state cannot approve the assessment report and related materials on the grounds of potential serious risk to the public health, the disputed points may eventually be referred to the European Commission, whose decision is binding on all member states. -21- Table of Contents We have obtained an orphan medicinal product designation in the E.U. from the EMA for Galafold ® for the treatment of Fabry disease and the combination product, Pombiliti ® + Opfolda ® , for the treatment of Pompe disease.
The MHRA has introduced changes to national licensing procedures, including procedures to prioritize access to new medicines that will benefit patients, an accelerated assessment procedure and new routes of evaluation for novel products and biotechnological products. All existing E.U. marketing authorizations ("MAs") for centrally authorized products were automatically converted ("grandfathered") into U.K. MAs free-of-charge on January 1, 2021.
The U.K. regulatory regime largely mirrors that of the E.U. -22- Table of Contents The MHRA has introduced changes to national licensing procedures, including procedures to prioritize access to new medicines that will benefit patients, an accelerated assessment procedure and new routes of evaluation for novel products and biotechnological products.
Currently, two products, both ERTs, are approved for the treatment of Pompe disease: alglucosidase alfa and avalglucosidase alfa-ngpt by Sanofi Aventis. -7- Table of Contents Strategic Alliances and Arrangements We will continue to evaluate business development opportunities to build stockholder value and provide us with access to the financial, technical, clinical, commercial resources, and intellectual property necessary to develop and market technologies or products in rare and orphan diseases.
Strategic Alliances and Arrangements We will continue to evaluate business development opportunities to build stockholder value and provide us with access to the financial, technical, clinical, commercial resources, and intellectual property necessary to develop and market technologies or products in rare and orphan diseases. We are exploring potential collaborations, alliances, and various other business development opportunities on a regular basis.
Signs and symptoms of Pompe disease can be severe and debilitating and include progressive muscle weakness throughout the body, particularly the heart and skeletal muscles. GAA deficiency causes accumulation of glycogen in cells, which is believed to result in the clinical manifestations of Pompe disease.
Pompe Disease Background Pompe disease is a lysosomal storage disorder that results from a deficiency in an enzyme, GAA. Signs and symptoms of Pompe disease can be severe and debilitating and include progressive muscle weakness throughout the body, particularly the heart and skeletal muscles.
Additionally, we strive to attract and retain the most talented employees in the industry and across -23- Table of Contents the globe by offering competitive compensation and benefits that support their health, financial and emotional well-being.
Additionally, we strive to attract and retain the most talented employees in the industry and across the globe by offering competitive compensation and benefits that support their health, financial and emotional well-being. Our compensation philosophy is based on rewarding each employee’s individual contributions and striving to achieve equal pay for equal work regardless of gender, race or ethnicity.
Miglustat is not an active ingredient that contributes directly to glycogen reduction. In addition, clinical studies are ongoing in pediatric patients for both the LOPD and infantile-onset Pompe disease ("IOPD") populations. Next-Generation for Pompe Disease We are committed to continued innovation for all people living with Pompe disease.
Miglustat binds to and stabilizes the cipaglucosidase alfa-atga in circulation reducing inactivation of rhGAA in circulation to improve the uptake of active enzyme into key disease relevant tissues. Miglustat is not an active ingredient that contributes directly to glycogen reduction. In addition, clinical studies are ongoing in pediatric patients for both the LOPD and infantile-onset Pompe disease ("IOPD") populations.
Following designation, the applicant is expected to complete a clinical development program within a reasonable time period, in order to continue with an application under the EAMS. In January 2020, the MHRA issued a PIM designation for AT-GAA for the treatment of late-onset Pompe disease and subsequently granted a positive opinion under EAMS in June 2021.
Following designation, the applicant is expected to complete a clinical development program within a reasonable time period, in order to continue with an application under the EAMS. We have obtained orphan drug designation in Japan for migalastat for the treatment of Fabry Disease.
A 30-day review period after the submission and receipt of an IND is required prior to the commencement of clinical testing in humans. The IND becomes effective 30 days after its receipt by the FDA, and trials may begin at that point unless the FDA notifies the sponsor that the investigations are subject to a clinical hold.
The IND becomes effective 30 days after its receipt by the FDA, and trials may begin at that point unless the FDA notifies the sponsor that the investigations are subject to a clinical hold. Clinical trials usually involve the administration of the investigational new drug to healthy volunteers or patients under the supervision of a qualified investigator.
In addition, our trade secrets may otherwise become known or be discovered independently by others. To the extent that our consultants, contractors, or collaborators use intellectual property owned by others in their work for us, disputes may arise as to the rights in related or resulting know-how and inventions.
To the extent that our consultants, contractors, or collaborators use intellectual property owned by others in their work for us, disputes may arise as to the rights in related or resulting know-how and inventions. -10- Table of Contents Collaboration and License Agreements We have acquired rights to develop and commercialize our product candidates through licenses granted by various parties.
Enforcement actions may be brought by the Department of Justice or the SEC, and recent enacted legislation has expanded the SEC’s power to seek disgorgement in all FCPA cases filed in federal court and extended the statute of limitations in SEC enforcement actions in intent-based claims such as those under the FCPA from five years to ten years.
Enforcement actions may be brought by the Department of Justice or the SEC, and recent enacted legislation has expanded the SEC’s power to seek disgorgement in all FCPA cases filed in federal court and extended the statute of limitations in SEC enforcement actions in intent-based claims such as those under the FCPA from five years to ten years. -23- Table of Contents United States Healthcare Reform The United States and many foreign jurisdictions have enacted or proposed legislative and regulatory changes affecting the healthcare system, including implementing cost-containment programs to limit the growth of government-paid healthcare costs, including price controls, restrictions on reimbursement and requirements for substitution of generic products for branded prescription drugs.
Amicus has completed the necessary baseline submission for conversion and was granted Marketing Authorization on August 4, 2021 for Galafold ® with an effective date of January 1, 2021. -21- Table of Contents There is no pre-marketing authorization orphan designation. Instead, the MHRA reviews applications for orphan designation in parallel to the corresponding MA application.
All existing E.U. marketing authorizations ("MAs") for centrally authorized products were automatically converted ("grandfathered") into U.K. MAs free-of-charge on January 1, 2021. Amicus has completed the necessary baseline submission for conversion and was granted Marketing Authorization on August 4, 2021 for Galafold ® with an effective date of January 1, 2021. There is no pre-marketing authorization orphan designation.
Any patents issuing from these pending applications will expire between 2033 and 2043. We also filed Patent Term Extension application at the U.S.
Any patents issuing from these pending applications will expire between 2033 and 2043. We also filed Patent Term Extension application at the U.S. Patent and Trademark Office ("USPTO"), requesting that the term of certain issued U.S. patent covering cipaglucosidase alfa, the active pharmaceutical ingredient in Pombiliti ® , be extended pursuant to 35 U.S.C. § 156.
All promotional materials for drug candidates approved under accelerated regulations are subject to prior review by the FDA. Section 505(b)(2) New Drug Applications Most drug products obtain FDA marketing approval pursuant to an NDA, an ANDA, or a BLA.
All promotional materials for drug candidates approved under accelerated regulations are subject to prior review by the FDA.
Pombiliti ® + Opfolda ® consists of a uniquely engineered rhGAA enzyme, cipaglucosidase alfa-atga, with an optimized carbohydrate structure to enhance cellular uptake, administered intravenously in combination with orally administered miglustat. Miglustat binds to and stabilizes the cipaglucosidase alfa-atga in circulation reducing inactivation of rhGAA in circulation to improve the uptake of active enzyme into key disease relevant tissues.
Additional regulatory submissions and reimbursement processes with global health authorities are currently underway. Pombiliti ® + Opfolda ® consists of a uniquely engineered recombinant human acid alpha-glucosidase ("rhGAA") enzyme, cipaglucosidase alfa-atga, with an optimized carbohydrate structure to enhance cellular uptake, administered intravenously in combination with orally administered miglustat.
In late-onset Pompe disease, symptoms may not appear until late childhood or adulthood and patients often experience progressive muscle weakness. According to reported estimates of the Acid Maltase Deficiency Association, the United Pompe Foundation, and the Lysosomal Disease Program at Massachusetts General Hospital, there are 5,000-10,000 patients with Pompe disease worldwide.
According to reported estimates of the Acid Maltase Deficiency Association, the United Pompe Foundation, and the Lysosomal Disease Program at Massachusetts General Hospital, there are 5,000-10,000 patients with Pompe disease worldwide. Pompe disease is a rare genetic disease with a traditionally used incidence rate of 1:40,000 (European Journal of Human Genetics 1999).
Additionally, Pombiliti ® + Opfolda ® has been granted orphan drug designation or status in the U.S., U.K., Switzerland and Japan and data exclusivity in the E.U. Our Strategy Our strategy is to create, manufacture, test, and deliver the highest quality medicines for people living with rare diseases through internally developed, jointly developed, acquired, or in-licensed products and product candidates.
Additionally, Pombiliti ® + Opfolda ® has been granted orphan drug designation or status in the U.S., U.K., Switzerland and Japan and data exclusivity in the E.U.
Pombiliti ® + Opfolda ® was approved by the EC, the MHRA and the FDA in 2023, and the Swissmedic in 2024 for adult late-onset Pompe disease ("LOPD") patients. Additional regulatory submissions and reimbursement processes with global health authorities are currently underway.
Pombiliti ® + Opfolda ® was approved by the European Commission ("EC"), the Medicines and Healthcare products Regulatory Agency ("MHRA"), and the Food and Drug Administration ("FDA") in 2023, the Swissmedic and the Therapeutics Good Administration in Australia in 2024, and Health Canada and Japan's Ministry of Health, Labor and Welfare in 2025 for adult late-onset Pompe disease ("LOPD") patients.
In November 2022, we filed four lawsuits against Teva, Lupin, and Aurobindo in the U.S. District Court for the District of Delaware for infringement of our Orange Book-listed patents and will vigorously enforce our Galafold ® intellectual property rights. Lupin, Aurobindo and Teva supplemented their Paragraph IV Certifications in 2023.
District Court for the District of Delaware (the "District Court") for infringement of our Orange Book-listed patents. Lupin, Aurobindo, and Teva supplemented their Paragraph IV Certifications in 2023. In the fourth quarter of 2023, a stipulation order to stay litigation with respect to Lupin was ordered.
We are leveraging our global capabilities to develop and broaden our franchises in Fabry and Pompe disease, with focused discovery work on next-generation therapies and novel technologies. Highlights of our progress include: • Commercial success in Fabry disease .
Our Strategy Our strategy is to create, manufacture, test, and deliver the highest quality medicines for people living with rare diseases through internally developed, jointly developed, acquired, or in-licensed products and product candidates. We are leveraging our global capabilities to develop and broaden our franchises in Fabry and Pompe disease, with focused discovery work on next-generation therapies and novel technologies.
Once granted, product approvals may be withdrawn if compliance with regulatory standards is not maintained, problems are identified following initial marketing, or post-marketing commitments are not met. -14- Table of Contents The Hatch-Waxman Act In seeking approval for a drug through an NDA, applicants are required to list with the FDA certain patent(s) with claims that cover the applicant's product or approved method of use.
Once granted, product approvals may be withdrawn if compliance with regulatory standards is not maintained, problems are identified following initial marketing, or post-marketing commitments are not met. In September 2025, the FDA issued draft guidance on the importance of post-approval safety and efficacy data for gene therapies.
Any reduction in reimbursement from Medicare, Medicaid, or other government programs may result in a similar reduction in payments from private payers. The Inflation Reduction Act of 2022 (the "IRA") contains substantial drug pricing reforms, including the establishment of a drug price negotiation program within the U.S.
Any reduction in reimbursement from Medicare, Medicaid, or other government programs may result in a similar reduction in payments from private payers. As an alternative to the Affordable Care Act, the Great Healthcare Plan was recently announced.
The FDA may also require companies to perform additional studies or measurements to support the change from the approved product.
The FDA may also require companies to perform additional studies or measurements to support the change from the approved product. The FDA may then approve the new product candidate for all or some of the label indications for which the referenced product has been approved, as well as for any new indication sought by the Section 505(b)(2) applicant.
(2) Reflects revenue for the twelve-month period ended December 31, 2024, as Takeda's fiscal year ends on March 31, 2025. (3) Reflects revenue for the twelve-month period ended September 30, 2024. Government Regulation FDA Approval Process In the U.S., biopharmaceutical products, including gene therapies, are subject to extensive regulation by the FDA.
(2) In addition to the competitors listed in the table, we are aware of several companies pursuing early stage clinical development of gene therapies for Fabry and Pompe disease. Government Regulation FDA Approval Process In the U.S., biopharmaceutical products, including gene therapies, are subject to extensive regulation by the FDA.
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Item 1. BUSINESS Overview We are a global, patient-dedicated biotechnology company focused on discovering, developing, and delivering novel medicines for rare diseases. We seek to deliver the highest quality therapies that have the potential to obsolete current treatments, provide significant benefits to patients, and be first- or best-in-class.
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Item 1. BUSINESS Overview We are a leading, global biotechnology company with a clear and compelling mission to develop and deliver transformative medicines for people living with rare diseases. With extraordinary patient focus, we strive to redefine expectations in rare disease.
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For the year ended December 31, 2024, Pombiliti ® + Opfolda ® revenue was $70.2 million of consolidated revenue. Pombiliti ® + Opfolda ® were approved by the European Commission ("EC"), the Medicines and Healthcare products Regulatory Agency ("MHRA)" of the United Kingdom, and the U.S. Food and Drug Administration ("FDA") in 2023 and the Swissmedic of Switzerland in 2024.
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On April 30, 2025, we entered into an exclusive license agreement with Dimerix Bioscience Pty Limited ("Dimerix") for the U.S. commercialization rights of Dimerix' Phase 3 drug candidate, DMX-200 for treatment of Focal Segmental Glomerulosclerosis ("FSGS") and other indications. On December 19, 2025, we entered into a definitive merger agreement (the "Merger Agreement") with BioMarin Pharmaceutical Inc.
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Additionally, in 2024, we established reimbursement agreements in multiple E.U. countries, including Spain, Czechia, Italy, Switzerland, and Sweden. • Pipeline advancement and growth. We are leveraging our global capabilities to develop and broaden our franchises in Fabry and Pompe disease, with focused discovery work on next-generation therapies and novel technologies. • Financial strength.
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Under the terms of the Merger Agreement, and in accordance with the General Corporation Law of the State of Delaware (the "DGCL"), if the transaction is completed, BioMarin's wholly owned acquisition subsidiary will merge with and into Amicus (the "Merger"), and Amicus will continue as the surviving corporation as a wholly owned subsidiary of BioMarin.

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

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Biggest changeThe new presidential administration has indicated a number of potential reforms that could have a material adverse effect on our business, future revenue, and results of operations, including changes impacting the FDA and the scope of its authority, imposition of significant tariffs on numerous countries (including the PRC, which is currently the sole supplier of Pombiliti ® ), and other, unforeseen developments that typically accompany a new presidential administration While it is impossible to predict future legislative or administrative actions, similar trade restrictions and regulatory changes could result in additional requirements for commercialization for our approved products and development of our product candidates, an increase in the cost of goods required to make our medicines, or otherwise impair, impede or frustrate our ability to deliver medicines globally. -63- Table of Contents The price of our common stock may be volatile and fluctuate substantially, which could result in substantial losses for purchasers of our common stock.
Biggest changeThe current presidential administration has indicated a number of potential reforms that could have a material adverse effect on our business, future revenue, and results of operations, including changes impacting the FDA and the scope of its authority, imposition of significant tariffs on numerous countries (including the PRC, which is a primary supplier of Pombiliti ® ), instituting a "most favored nation" policy requiring pharmaceutical companies to lower U.S. drug prices to match the lowest prices such drugs are sold for in other developed countries, and other, unforeseen developments that typically accompany a new presidential administration While it is impossible to predict future legislative or administrative actions, similar trade restrictions and regulatory changes could result in additional requirements for commercialization for our approved products and -66- Table of Contents development of our product candidates, an increase in the cost of goods required to make our medicines, or otherwise impair, impede or frustrate our ability to deliver medicines globally.
The risks that we may be subject to in possible future collaborations include the following: • collaborators have significant discretion in determining the efforts and resources that they will apply to these collaborations; • collaborators may fail to fulfill their contractual obligations; • we may be unable to retain collaborators who are qualified to assist in the development and commercialization of our products or product candidates; • collaborators may not pursue development and commercialization of our products or 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 diverts resources or creates 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 independently develop, or develop with third parties, products that compete directly or indirectly with our products or product candidates if 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; • a collaborator with marketing and distribution rights to one or more products may not commit sufficient resources to the marketing and distribution of such product or products; • 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 intellectual property or proprietary information or expose us to potential liability; • collaborators may infringe the intellectual property rights of third parties, which may expose us to litigation and potential liability; • disputes may arise between the collaborator and us as to the ownership of intellectual property arising during the collaboration; • we may grant rights to our collaborators to be the holder of any marketing authorizations in a jurisdiction, which could impact our ability to successfully commercialize our products; • we may grant exclusive rights to our collaborators, which would prevent us from collaborating with others; • disputes may arise between the collaborators and us that result in the delay or termination of the research, development or commercialization of our products or product candidates or that result in costly litigation or arbitration that diverts management attention and resources; and -44- Table of Contents • collaborations may be terminated and, if terminated, may result in a need for additional capital to pursue further development or commercialization of the applicable product candidates.
The risks that we may be subject to in possible future collaborations include the following: • collaborators have significant discretion in determining the efforts and resources that they will apply to these collaborations; • collaborators may fail to fulfill their contractual obligations; • we may be unable to retain collaborators who are qualified to assist in the development and commercialization of our products or product candidates; • collaborators may not pursue development and commercialization of our products or 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 diverts resources or creates 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; -47- Table of Contents • collaborators could independently develop, or develop with third parties, products that compete directly or indirectly with our products or product candidates if 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; • a collaborator with marketing and distribution rights to one or more products may not commit sufficient resources to the marketing and distribution of such product or products; • 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 intellectual property or proprietary information or expose us to potential liability; • collaborators may infringe the intellectual property rights of third parties, which may expose us to litigation and potential liability; • disputes may arise between the collaborator and us as to the ownership of intellectual property arising during the collaboration; • we may grant rights to our collaborators to be the holder of any marketing authorizations in a jurisdiction, which could impact our ability to successfully commercialize our products; • we may grant exclusive rights to our collaborators, which would prevent us from collaborating with others; • disputes may arise between the collaborators and us that result in the delay or termination of the research, development or commercialization of our products or product candidates or that result in costly litigation or arbitration that diverts management attention and resources; and • collaborations may be terminated and, if terminated, may result in a need for additional capital to pursue further development or commercialization of the applicable product candidates.
The review processes and the processes of regulatory authorities, including the FDA, EMA and PMDA, are extensive, lengthy, expensive, and uncertain, and such regulatory authorities may delay, limit, or deny the approval of any of our product candidates for many reasons, including, but not limited to: • our failure to demonstrate to the satisfaction of the applicable regulatory authorities that any of our product candidates, are safe and effective for a particular indication; • the results of clinical trials may not meet the level of statistical significance or other efficacy or safety parameters required by the applicable regulatory authorities for approval; • the applicable regulatory authority may disagree with the number, design, size, conduct, or implementation of our clinical trials or conclude that the data fail to meet statistical or clinical significance; • the applicable regulatory authority may not find the data from preclinical studies and clinical trials sufficient to demonstrate that the product candidate's clinical and other benefits outweigh its safety risks; • the applicable regulatory authority may disagree with our interpretation of data from preclinical studies or clinical trials, and may reject conclusions from preclinical studies or clinical trials, determine that primary or secondary endpoints from clinical trials were not met, or reject safety conclusions from such studies or trials; • the applicable regulatory authority may not accept data generated at one or more of our clinical trial sites; -26- Table of Contents • the applicable regulatory authority may determine that we did not properly oversee our clinical trials or follow the regulatory authority's advice or recommendations in designing and conducting our clinical trials; • an advisory committee, if convened by the applicable regulatory authority, may recommend against approval of our application or may recommend that the applicable regulatory authority require, as a condition of approval, additional preclinical studies or clinical trials, limitations on approved labeling or distribution and use restrictions, or even if an advisory committee, if convened, makes a favorable recommendation, the respective regulatory authority may still not approve the product candidate; • the applicable regulatory authority may only approve a limited label for less than the full indicated population, as a second line or rescue therapy, or impose other label restrictions; and • the applicable regulatory authority may identify deficiencies in the chemistry, manufacturing, and control sections of our application, our manufacturing processes, facilities, or analytical methods or those of our third-party contract manufacturers or be unable to complete any necessary manufacturing inspections of our third-party manufacturers which may lead to significant delays in the approval of our product candidates or to the rejection of our applications altogether.
The review processes and the processes of regulatory authorities, including the FDA, EMA and PMDA, are extensive, lengthy, expensive, and uncertain, and such regulatory authorities may delay, limit, or deny the approval of any of our product candidates for many reasons, including, but not limited to: • our failure to demonstrate to the satisfaction of the applicable regulatory authorities that any of our product candidates, are safe and effective for a particular indication; • the results of clinical trials may not meet the level of statistical significance or other efficacy or safety parameters required by the applicable regulatory authorities for approval; • the applicable regulatory authority may disagree with the number, design, size, conduct, or implementation of our clinical trials or conclude that the data fail to meet statistical or clinical significance; • the applicable regulatory authority may not find the data from preclinical studies and clinical trials sufficient to demonstrate that the product candidate's clinical and other benefits outweigh its safety risks; • the applicable regulatory authority may disagree with our interpretation of data from preclinical studies or clinical trials, and may reject conclusions from preclinical studies or clinical trials, determine that primary or secondary endpoints from clinical trials were not met, or reject safety conclusions from such studies or trials; • the applicable regulatory authority may not accept data generated at one or more of our clinical trial sites; • the applicable regulatory authority may determine that we did not properly oversee our clinical trials or follow the regulatory authority's advice or recommendations in designing and conducting our clinical trials; • an advisory committee, if convened by the applicable regulatory authority, may recommend against approval of our application or may recommend that the applicable regulatory authority require, as a condition of approval, additional preclinical studies or clinical trials, limitations on approved labeling or distribution and use restrictions, or even if an advisory committee, if convened, makes a favorable recommendation, the respective regulatory authority may still not approve the product candidate; • the applicable regulatory authority may only approve a limited label for less than the full indicated population, as a second line or rescue therapy, or impose other label restrictions; and -29- Table of Contents • the applicable regulatory authority may identify deficiencies in the chemistry, manufacturing, and control sections of our application, our manufacturing processes, facilities, or analytical methods or those of our third-party contract manufacturers or be unable to complete any necessary manufacturing inspections of our third-party manufacturers which may lead to significant delays in the approval of our product candidates or to the rejection of our applications altogether.
To the extent that any disruptions or security breach were to result in a loss or damage to our data or applications, or inappropriate disclosure of confidential or proprietary information, we could incur significant unexpected losses, expenses and liabilities, we could face litigation or suffer reputational harm and the further development of our product candidates could be delayed. -60- Table of Contents In addition, cybersecurity threats and reported incidents are increasing in their frequency, sophistication and intensity, including as a result of ongoing military conflicts, certain U.S. foreign relations, and increased remote work arrangements, and are becoming increasingly difficult to detect, particularly when they impact vendors, customers or suppliers, and other companies in our supply chain.
To the extent that any disruptions or security breach were to result in a loss or damage to our data or applications, or inappropriate disclosure of confidential or proprietary information, we could incur significant unexpected losses, expenses and liabilities, we could face litigation or suffer reputational harm and the further development of our product candidates could be delayed. -63- Table of Contents In addition, cybersecurity threats and reported incidents are increasing in their frequency, sophistication and intensity, including as a result of ongoing military conflicts, certain U.S. foreign relations, and increased remote work arrangements, and are becoming increasingly difficult to detect, particularly when they impact vendors, customers or suppliers, and other companies in our supply chain.
If the results of these trials or tests are not positive or are only modestly positive; or if there are safety concerns, we may: • choose not to seek regulatory approval in the U.S., E.U., U.K., or other key jurisdictions; • be delayed in obtaining marketing approval for our product candidates; • not obtain marketing approval at all; • obtain approval for indications or patient populations that are not as broad as intended or desired; -38- Table of Contents • obtain approval with labeling that includes significant use or distribution restrictions or safety warnings, including boxed warnings; • be subject to additional post-marketing testing requirements, safety strategies or restrictions, such as a requirement of a risk evaluation and mitigation strategy, or REMS; or • have the product removed from the market after obtaining regulatory approval.
If the results of these trials or tests are not positive or are only modestly positive; or if there are safety concerns, we may: -41- Table of Contents • choose not to seek regulatory approval in the U.S., E.U., U.K., or other key jurisdictions; • be delayed in obtaining marketing approval for our product candidates; • not obtain marketing approval at all; • obtain approval for indications or patient populations that are not as broad as intended or desired; • obtain approval with labeling that includes significant use or distribution restrictions or safety warnings, including boxed warnings; • be subject to additional post-marketing testing requirements, safety strategies or restrictions, such as a requirement of a risk evaluation and mitigation strategy, or REMS; or • have the product removed from the market after obtaining regulatory approval.
Moreover, because we are incorporated in Delaware, we are governed by the provisions of Section 203 of the Delaware General Corporation Law, which prohibits a person who owns in excess of 15% of our outstanding voting stock from merging or combining with us for a period of three years after the date of the transaction in which the person acquired in excess of 15% of our outstanding voting stock, unless the merger or combination is approved in a prescribed manner. -62- Table of Contents Unfavorable global economic conditions, whether brought about by material global crises, health epidemics, military conflicts or war, geopolitical and trade disputes or other factors, may adversely affect our business and financial results.
Moreover, because we are incorporated in Delaware, we are governed by the provisions of Section 203 of the Delaware General Corporation Law, which prohibits a person who owns in excess of 15% of our outstanding voting stock from merging or combining with us for a period of three years after the date of the transaction in which the person acquired in excess of 15% of our outstanding voting stock, unless the merger or combination is approved in a prescribed manner. -65- Table of Contents Unfavorable global economic conditions, whether brought about by material global crises, health epidemics, military conflicts or war, geopolitical and trade disputes or other factors, may adversely affect our business and financial results.
Even if we are able to establish and maintain arrangements with third-party manufacturers, reliance on third-party manufacturers entails additional risks, including: -41- Table of Contents • reliance on the third party for regulatory compliance and quality assurance, including with their own vendors with which we do not have a contractual relationship; • limitations on supply availability resulting from capacity, scheduling constraints, and geographic of the third parties; • inability to manufacture product that meets the regulatory requirements for product approval; • inability to manufacture batches that meet specifications and quality standards; • inability to hire and retain the skilled workers necessary to manufacture our products; • inability to meet environmental sustainability requirements; • impact on our reputation in the marketplace if manufacturers of our products, once commercialized, fail to meet the demands of our customers; • the possible breach of the manufacturing agreement by the third party; • the possible misappropriation of our proprietary information, including our trade secrets and know-how; • the high cost of manufacturing processes and raw materials; and • the possible termination or nonrenewal of the agreement by the third party at a time that is costly or inconvenient for us.
Even if we are able to establish and maintain arrangements with third-party manufacturers, reliance on third-party manufacturers entails additional risks, including: • reliance on the third party for regulatory compliance and quality assurance, including with their own vendors with which we do not have a contractual relationship; • limitations on supply availability resulting from capacity, scheduling constraints, and geographic of the third parties; • inability to manufacture product that meets the regulatory requirements for product approval; • inability to manufacture batches that meet specifications and quality standards; • inability to hire and retain the skilled workers necessary to manufacture our products; • inability to meet environmental sustainability requirements; • impact on our reputation in the marketplace if manufacturers of our products, once commercialized, fail to meet the demands of our customers; • the possible breach of the manufacturing agreement by the third party; • the possible misappropriation of our proprietary information, including our trade secrets and know-how; • the high cost of manufacturing processes and raw materials; and • the possible termination or nonrenewal of the agreement by the third party at a time that is costly or inconvenient for us.
Regardless of merit or eventual outcome, liability claims may result in: • reduced resources of our management to pursue our business strategy; • decreased demand for any product candidates or products that we may develop; • injury to our reputation and significant negative media attention; -32- Table of Contents • regulatory investigations, prosecutions, or enforcement actions that could require costly recalls or product modifications; • withdrawal of clinical trial participants; • regulatory authorities placing ongoing clinical trials on clinical hold; • significant costs to defend the related litigation; • increased insurance costs or an inability to maintain appropriate insurance coverage; • substantial monetary awards to trial participants or patients, including awards that substantially exceed our product liability insurance, which we would then be required to pay from other sources, if available, and would damage our ability to obtain liability insurance at reasonable costs, or at all, in the future; • loss of revenue; and • the inability to commercialize any products that we may develop.
Regardless of merit or eventual outcome, liability claims may result in: • reduced resources of our management to pursue our business strategy; • decreased demand for any product candidates or products that we may develop; • injury to our reputation and significant negative media attention; • regulatory investigations, prosecutions, or enforcement actions that could require costly recalls or product modifications; • withdrawal of clinical trial participants; • regulatory authorities placing ongoing clinical trials on clinical hold; • significant costs to defend the related litigation; • increased insurance costs or an inability to maintain appropriate insurance coverage; • substantial monetary awards to trial participants or patients, including awards that substantially exceed our product liability insurance, which we would then be required to pay from other sources, if available, and would damage our ability to obtain liability insurance at reasonable costs, or at all, in the future; • loss of revenue; and • the inability to commercialize any products that we may develop.
Factors that may inhibit our efforts to successfully commercialize Galafold ® , Pombiliti ® + Opfolda ® , or our product candidates if and when they are approved by regulatory authorities, on our own include: • our inability to recruit, train, and retain adequate numbers of effective sales and marketing personnel; • the inability of sales personnel to obtain access to adequate numbers of physicians to prescribe our products; • the lack of complementary products to be offered by sales personnel, which may put us at a competitive disadvantage relative to companies with more extensive product lines; • unforeseen costs and expenses associated with creating an independent sales and marketing organization; -27- Table of Contents • misconduct by independent sales and marketing organizations that expose us to fines, penalties and other restrictions on our ability to effectively market and sell our products; and • efforts by our competitors to commercialize products at or about the time when our product candidates would be coming to market.
Factors that may inhibit our efforts to successfully commercialize Galafold ® , Pombiliti ® + Opfolda ® , or our product candidates if and when they are approved by regulatory authorities, on our own include: • our inability to recruit, train, and retain adequate numbers of effective sales and marketing personnel; • the inability of sales personnel to obtain access to adequate numbers of physicians to prescribe our products; • the lack of complementary products to be offered by sales personnel, which may put us at a competitive disadvantage relative to companies with more extensive product lines; • unforeseen costs and expenses associated with creating an independent sales and marketing organization; • misconduct by independent sales and marketing organizations that expose us to fines, penalties and other restrictions on our ability to effectively market and sell our products; and • efforts by our competitors to commercialize products at or about the time when our product candidates would be coming to market.
The Company intends to continue to vigorously defend its patent rights, both domestically and internationally; however, the outcome of such matters cannot be predicted with certainty. -54- Table of Contents Third parties may initiate legal proceedings alleging that we are infringing their intellectual property rights, the outcome of which would be uncertain and could have a material adverse effect on the success of our business.
The Company intends to continue to vigorously defend its patent rights, both domestically and internationally; however, the outcome of such matters cannot be predicted with certainty. -57- Table of Contents Third parties may initiate legal proceedings alleging that we are infringing their intellectual property rights, the outcome of which would be uncertain and could have a material adverse effect on the success of our business.
We may not be able to accomplish these tasks, and our failure to accomplish any of them could prevent us from successfully growing our company. -57- Table of Contents Our employees, independent contractors, principal investigators, CROs, consultants, agents, and vendors may engage in misconduct or other improper activities, including noncompliance with regulatory standards and requirements, which could cause significant liability for us and harm our reputation.
We may not be able to accomplish these tasks, and our failure to accomplish any of them could prevent us from successfully growing our company. -60- Table of Contents Our employees, independent contractors, principal investigators, CROs, consultants, agents, and vendors may engage in misconduct or other improper activities, including noncompliance with regulatory standards and requirements, which could cause significant liability for us and harm our reputation.
Our future funding requirements, both near and long-term, will depend on many factors, including, but not limited to: • the costs of commercialization activities, including maintaining sales, marketing, and distribution capabilities for Galafold ® , Pombiliti ® + Opfolda ® , and any product candidates for which we may receive regulatory approval in regions where we choose to commercialize our products on our own; • the scope, progress, results, and costs of preclinical development, laboratory testing, and clinical trials for our product candidates and any other product candidates that we may in-license or acquire; • the cost of manufacturing drug supply for our preclinical studies, clinical trials, and commercial supply, including the significant cost of manufacturing Pombiliti ® + Opfolda ® and our gene therapies; • the outcome, timing, and cost of the regulatory approval process by the FDA, EMA, PMDA, and other foreign regulatory authorities, including the potential for regulatory authorities to delay approvals pending site inspections or requiring that we perform more studies than those that we currently anticipate for our products and product candidates; • the outcome and timing of the reimbursement and pricing approvals by the applicable authorities in the jurisdictions we are seeking to commercialize our products; • the activities of our competitors; -48- Table of Contents • the cost of filing, prosecuting, defending, and enforcing any patent claims and other intellectual property rights; • the cost and timing of completion of existing or expanded commercial-scale outsourced manufacturing activities; • the cost of defending any claims asserted against us or prosecuting any claims we may assert against others; • the impact of, and cost of complying with new laws, rules, regulations or executive orders in the geographies in which we or our key manufacturers, suppliers and customers operate; • the emergence of competing technologies and other adverse market developments; • the impact of foreign exchange rates on our operating expenses and revenue projections; and • the extent to which we acquire or invest in additional businesses, products, and technologies.
Our future funding requirements, both near and long-term, will depend on many factors, including, but not limited to: • the costs of commercialization activities, including maintaining sales, marketing, and distribution capabilities for Galafold ® , Pombiliti ® + Opfolda ® , and any product candidates for which we may receive regulatory approval in regions where we choose to commercialize our products on our own, including DMX-200 in the U.S.; • the scope, progress, results, and costs of preclinical development, laboratory testing, and clinical trials for our product candidates and any other product candidates that we may in-license or acquire; • the cost of manufacturing drug supply for our preclinical studies, clinical trials, and commercial supply, including the significant cost of manufacturing Pombiliti ® + Opfolda ® and our gene therapies; -51- Table of Contents • the outcome, timing, and cost of the regulatory approval process by the FDA, EMA, PMDA, and other foreign regulatory authorities, including the potential for regulatory authorities to delay approvals pending site inspections or requiring that we perform more studies than those that we currently anticipate for our products and product candidates; • the outcome and timing of the reimbursement and pricing approvals by the applicable authorities in the jurisdictions we are seeking to commercialize our products; • the activities of our competitors; • the cost of filing, prosecuting, defending, and enforcing any patent claims and other intellectual property rights; • the cost and timing of completion of existing or expanded commercial-scale outsourced manufacturing activities; • the cost of defending any claims asserted against us or prosecuting any claims we may assert against others; • the impact of, and cost of complying with new laws, rules, regulations or executive orders in the geographies in which we or our key manufacturers, suppliers and customers operate; • the emergence of competing technologies and other adverse market developments; • the impact of foreign exchange rates on our operating expenses and revenue projections; and • the extent to which we acquire or invest in additional businesses, products, and technologies.
The degree of market acceptance of our product candidates, if approved for commercial sale, will depend on a number of factors, including: • the efficacy and potential advantages compared to competitive or alternative treatments, including generics and gene therapies; • the prevalence and severity of any side effects; • the ability to offer our products and product candidates, if approved, for sale at competitive prices; • convenience and ease of administration compared to alternative treatments; • the willingness of the target patient population to try new therapies and of physicians to prescribe these therapies; • the strength of marketing and distribution support and timing of market introduction of competitive products; • publicity concerning our products or competing products and treatments; • competition from other products for the same or similar indications; and • sufficient third-party coverage or reimbursement.
The degree of market acceptance of our product candidates, if approved for commercial sale, will depend on a number of factors, including: -31- Table of Contents • the efficacy and potential advantages compared to competitive or alternative treatments, including generics and gene therapies; • the prevalence and severity of any side effects; • the ability to offer our products and product candidates, if approved, for sale at competitive prices; • convenience and ease of administration compared to alternative treatments; • the willingness of the target patient population to try new therapies and of physicians to prescribe these therapies; • the strength of marketing and distribution support and timing of market introduction of competitive products; • publicity concerning our products or competing products and treatments; • competition from other products for the same or similar indications; and • sufficient third-party coverage or reimbursement.
Starting in October 2022, we received Paragraph IV Notice letters from Aurobindo Pharma Ltd. (along with their applicable affiliates, “Aurobindo”), Lupin Ltd. (along with their applicable affiliates, “Lupin”), and Teva Pharmaceutical, Inc.
In October 2022, we received Paragraph IV Notice letters from Aurobindo Pharma Ltd. (along with their applicable affiliates, “Aurobindo”), Lupin Ltd. (along with their applicable affiliates, “Lupin”), and Teva Pharmaceutical, Inc.
Finally, in October 2023, we entered into a securities purchase agreement with Blackstone for the private placement of 2,467,104 shares of our common stock, at a purchase price of $12.16 per share. We may fail to qualify for continued listing on The NASDAQ Global Market which could make it more difficult for investors to sell their shares.
Additionally, in October 2023, we entered into a securities purchase agreement with Blackstone for the private placement of 2,467,104 shares of our common stock, at a purchase price of $12.16 per share. We may fail to qualify for continued listing on The NASDAQ Global Market which could make it more difficult for investors to sell their shares.
There have been significant ongoing judicial, administrative, executive, and legislative efforts to modify or eliminate the Affordable Care Act. -31- Table of Contents Changes to and under the Affordable Care Act remain possible but it is unknown what form any such changes or any law proposed to replace or revise the Affordable Care Act would take, and how or whether it may affect our business in the future.
There have been significant ongoing judicial, administrative, executive, and legislative efforts to modify or eliminate the Affordable Care Act. -34- Table of Contents Changes to and under the Affordable Care Act remain possible but it is unknown what form any such changes or any law proposed to replace or revise the Affordable Care Act would take, and how or whether it may affect our business in the future.
Litigation may be necessary to defend against these claims. -55- Table of Contents In addition, while we typically require our employees and contractors who may be involved in the development of intellectual property to execute agreements assigning such intellectual property to us, we may be unsuccessful in executing such an agreement with each party who in fact develops intellectual property that we regard as our own.
Litigation may be necessary to defend against these claims. -58- Table of Contents In addition, while we typically require our employees and contractors who may be involved in the development of intellectual property to execute agreements assigning such intellectual property to us, we may be unsuccessful in executing such an agreement with each party who in fact develops intellectual property that we regard as our own.
If we fail to retain our qualified personnel or replace them when they leave, we may be unable to recruit replacements without increased expense, if at all, or continue our development and commercialization activities. -56- Table of Contents In addition, we rely on consultants and advisors, including scientific and clinical advisors, to assist us in formulating our research and development and commercialization strategy.
If we fail to retain our qualified personnel or replace them when they leave, we may be unable to recruit replacements without increased expense, if at all, or continue our development and commercialization activities. -59- Table of Contents In addition, we rely on consultants and advisors, including scientific and clinical advisors, to assist us in formulating our research and development and commercialization strategy.
Applicable regulations of both the EMA and E.U. member states also impose liability for failing to comply with fraud and abuse laws or improperly using information obtained in in the course of clinical trials with the EMA or other regulatory authorities; -36- Table of Contents • U.S. federal Health Insurance Portability and Accountability Act of 1996 ("HIPAA") which imposes criminal liability and amends provisions on the reporting, investigation, enforcement, and penalizing of civil liability for executing a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters.
Applicable regulations of both the EMA and E.U. member states also impose liability for failing to comply with fraud and abuse laws or improperly using information obtained in in the course of clinical trials with the EMA or other regulatory authorities; • U.S. federal Health Insurance Portability and Accountability Act of 1996 ("HIPAA") which imposes criminal liability and amends provisions on the reporting, investigation, enforcement, and penalizing of civil liability for executing a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters.
Therefore, we cannot know with certainty whether we were the first to make the inventions claimed in our patents or pending patent applications, or that we were the first to file for patent protection of such inventions. -52- Table of Contents Additionally, we may be subject to a third-party pre-issuance submission of prior art to the U.S.
Therefore, we cannot know with certainty whether we were the first to make the inventions claimed in our patents or pending patent applications, or that we were the first to file for patent protection of such inventions. -55- Table of Contents Additionally, we may be subject to a third-party pre-issuance submission of prior art to the U.S.
If our policies, procedures, and compliance systems, including our Enterprise Risk Management Program and the Global Risk Committee are not effective, or if we are not successful in monitoring or evaluating the risks to which we are or may be -58- Table of Contents exposed, our business, reputation, financial condition and operating results could be materially adversely affected.
If our policies, procedures, and compliance systems, including our Enterprise Risk Management Program and the Global Risk Committee are not effective, or if we are not successful in monitoring or evaluating the risks to which we are or may be -61- Table of Contents exposed, our business, reputation, financial condition and operating results could be materially adversely affected.
The degree of future protection for our proprietary rights is uncertain, and we cannot ensure that: • we or our licensors were the first to make the inventions covered by each of our pending patent applications; • we or our licensors were the first to file patent applications for these inventions; • others will not independently develop similar or alternative technologies or duplicate any of our technologies; • any patents issued to us or our licensors will provide a basis for commercially viable products, will provide us with any competitive advantages or will not be challenged by third parties; • licenses from other third parties will not be required to commercialize patented products; -51- Table of Contents • we will develop additional proprietary technologies that are patentable; • we will file patent applications for new proprietary technologies promptly or at all; • our patents will not expire prior to or shortly after commencing commercialization of a product; • the patents of others will not have a negative effect on our ability to do business; • patent authorities will not identify deficiencies in our patent applications and refuse to grant our patents; or • outcome of any patent litigation, including Hatch-Waxman litigation involving Galafold ® , or any possible future litigation involving Pombiliti ® + Opfolda ® , will demonstrate that our patents are valid and enforceable.
The degree of future protection for our proprietary rights is uncertain, and we cannot ensure that: • we or our licensors were the first to make the inventions covered by each of our pending patent applications; • we or our licensors were the first to file patent applications for these inventions; -54- Table of Contents • others will not independently develop similar or alternative technologies or duplicate any of our technologies; • any patents issued to us or our licensors will provide a basis for commercially viable products, will provide us with any competitive advantages or will not be challenged by third parties; • licenses from other third parties will not be required to commercialize patented products; • we will develop additional proprietary technologies that are patentable; • we will file patent applications for new proprietary technologies promptly or at all; • our patents will not expire prior to or shortly after commencing commercialization of a product; • the patents of others will not have a negative effect on our ability to do business; • patent authorities will not identify deficiencies in our patent applications and refuse to grant our patents; or • outcome of any patent litigation involving Galafold ® , or any possible future litigation involving Pombiliti ® + Opfolda ® , will demonstrate that our patents are valid and enforceable.
We also have several pending applications globally covering Galafold ® , Pombiliti ® + Opfolda ® and our gene therapy product candidates. There can be no assurance that these applications will be allowed, that allowed applications will be issued, or that the scope of such patents, if they issue, will be sufficient to protect our products.
We also have several pending applications globally covering Galafold ® , Pombiliti ® + Opfolda ® and our product candidates. There can be no assurance that these applications will be allowed, that allowed applications will be issued, or that the scope of such patents, if they issue, will be sufficient to protect our products.
Integration of an acquired company or assets may also disrupt ongoing operations, require the hiring of additional personnel and the implementation of additional internal systems and infrastructure, especially the acquisition of commercial assets, and require management resources that would otherwise focus on developing -61- Table of Contents our existing business.
Integration of an acquired company or assets may also disrupt ongoing operations, require the hiring of additional personnel and the implementation of additional internal systems and infrastructure, especially the acquisition of commercial assets, and require management resources that would otherwise focus on developing -64- Table of Contents our existing business.
State research and development credits will expire 2024 through 2033. Utilization of NOLs may be subject to a substantial limitation pursuant to Section 382 of the Internal Revenue Code of 1986, as amended ("Section 382"), as well as similar state statutes in the event of an ownership change.
State research and development credits will expire 2026 through 2033. Utilization of NOLs may be subject to a substantial limitation pursuant to Section 382 of the Internal Revenue Code of 1986, as amended ("Section 382"), as well as similar state statutes in the event of an ownership change.
The diseases that our product candidates and Galafold ® are intended to treat are characterized by small patient populations, which could result in slow enrollment of clinical trial participants. In addition, our competitors have ongoing clinical trials for product candidates that could be competitive with our product candidates.
The diseases that our product candidates, Galafold ® and Pombiliti ® + Opfolda ® are intended to treat are characterized by small patient populations, which could result in slow enrollment of clinical trial participants. In addition, our competitors have ongoing clinical trials for product candidates that could be competitive with our product candidates.
Failure to comply with these requirements could result in reputational risk, public reprimands, administrative penalties, fines, or imprisonment; • U.S. federal government price reporting laws, which require us to calculate and report complex pricing metrics to government programs, where such reported prices may be used in the calculation of reimbursement and/or discounts on our marketed drugs.
Failure to comply with these requirements could result in reputational risk, public reprimands, administrative penalties, fines, or imprisonment; -40- Table of Contents • U.S. federal government price reporting laws, which require us to calculate and report complex pricing metrics to government programs, where such reported prices may be used in the calculation of reimbursement and/or discounts on our marketed drugs.
It is currently unknown what impact, if any proposed changes by the federal and state governments in the U.S. and similar changes in foreign countries may have on pricing and reimbursement, particularly with respect to government programs such as Medicare and Medicaid and Pharmacy Benefit Managers for commercial plans, and including reimportation, reference pricing and limitations on manufacturer price increases.
It is currently unknown what impact, if any proposed changes by the federal and state governments in the U.S. and similar changes in foreign countries may have on pricing and reimbursement, particularly with respect to government programs such as Medicare and Medicaid and Pharmacy Benefit Managers for commercial plans, and including reimportation or parallel trade, reference pricing and limitations on manufacturer price increases.
Undesirable side effects caused by our products, Galafold ® and Pombiliti ® + Opfolda ® , or product candidates could interrupt, delay or halt clinical trials and could result in the withdrawal or denial of regulatory approval by the FDA, EMA or other regulatory authorities for any or all targeted indications, and in turn prevent us from commercializing our products or product candidates, if approved, and generating revenues from their sale.
Undesirable side effects caused by our products, Galafold ® and Pombiliti ® + Opfolda ® , or product candidates, including DMX-200, could interrupt, delay or halt clinical trials and could result in the withdrawal or denial of regulatory approval by the FDA, EMA or other regulatory authorities for any or all targeted indications, and in turn prevent us from commercializing our products or product candidates, if approved, and generating revenues from their sale.
Our inability to generate sufficient funds to satisfy our debt payment obligations or remain in compliance with the debt covenants may result in such obligations being accelerated by our lenders, which would likely have a material adverse effect on our business, financial condition and results of operations. -49- Table of Contents Foreign currency exchange rate fluctuations could harm our financial results.
Our inability to generate sufficient funds to satisfy our debt payment obligations or remain in compliance with the debt covenants may result in such obligations being accelerated by our lenders, which would likely have a material adverse effect on our business, financial condition and results of operations. Foreign currency exchange rate fluctuations could harm our financial results.
If we do enter into co-promote or out-licensing arrangements with third parties, our product revenues will be lower than if we directly sold and marketed our products and any revenues received under such arrangements will depend on the skills and efforts of others. We may not be successful in entering into distribution arrangements and marketing alliances with third parties.
If we do enter into co-promote or out-licensing arrangements with third parties, our product revenues will be lower than if we directly sold and marketed our products and any revenues received under such arrangements will depend on the skills and efforts of others. -30- Table of Contents We may not be successful in entering into distribution arrangements and marketing alliances with third parties.
Several other countries, including the U.K., have enacted similar anti-kickback, fraud and abuse, and healthcare laws and regulations; • U.S. federal False Claims Act, which imposes criminal and civil penalties, including through civil whistleblower or qui tam actions, against individuals or entities for knowingly presenting, or causing to be presented, to the federal government, claims for payment that are false or fraudulent or making a false statement to avoid, decrease or conceal an obligation to pay money to the federal government.
Several other countries, including the U.K., have enacted similar anti-kickback, fraud and abuse, and healthcare laws and regulations; -39- Table of Contents • U.S. federal False Claims Act, which imposes criminal and civil penalties, including through civil whistleblower or qui tam actions, against individuals or entities for knowingly presenting, or causing to be presented, to the federal government, claims for payment that are false or fraudulent or making a false statement to avoid, decrease or conceal an obligation to pay money to the federal government.
Any change in a CRO during an ongoing preclinical development activity or clinical trial could seriously delay that trial and potentially compromise the results of the activity or trial. -43- Table of Contents We may not be successful in maintaining or establishing collaborations, which could adversely affect our ability to develop and, particularly in international markets, commercialize products.
Any change in a CRO during an ongoing preclinical development activity or clinical trial could seriously delay that trial and potentially compromise the results of the activity or trial. We may not be successful in maintaining or establishing collaborations, which could adversely affect our ability to develop and, particularly in international markets, commercialize products.
As these tensions continue to rise, more targeted approaches by the U.S. or Chinese governments on certain products, industries or companies (including WuXi, a sole supplier of one of our products) could significantly impact our ability to effectively manufacture and distribute our products, including Pombiliti ® + Opfolda ® , materially impacting our ability to meet patient demands or financial forecasts.
As these tensions continue to rise, more targeted approaches by the U.S. or Chinese governments on certain products, industries or companies (including WuXi, the primary supplier of one of our products) could significantly impact our ability to effectively manufacture and distribute our products, including Pombiliti ® + Opfolda ® , materially impacting our ability to meet patient demands or financial forecasts.
Our ability to successfully commercialize Galafold ® , Pombiliti ® + Opfolda ® , or any product candidate if approved, will also depend in part on the extent to which coverage and reimbursement for these products and related treatments will be available from government health administration authorities, private health insurers and other organizations.
Our ability to successfully commercialize Galafold ® , Pombiliti ® + Opfolda ® , or any product candidate, including DMX-200, if approved, will also depend in part on the extent to which coverage and reimbursement for these products and related treatments will be available from government health administration authorities, private health insurers and other organizations.
In -59- Table of Contents addition, although our collaborators have environmental compliance processes in place, and we include oversight of these processes in our business reviews, they may not ultimately comply with these laws.
In -62- Table of Contents addition, although our collaborators have environmental compliance processes in place, and we include oversight of these processes in our business reviews, they may not ultimately comply with these laws.
Our inability to enroll a sufficient number of patients in any of our clinical trials would result in significant delays or may require us to abandon one or more clinical trials altogether. We may not be able to obtain or maintain orphan drug exclusivity for our products or product candidates.
Our inability to enroll a sufficient number of patients in any of our clinical trials would result in significant delays or may require us to abandon one or more clinical trials altogether. -43- Table of Contents We may not be able to obtain or maintain orphan drug exclusivity for our products or product candidates.
We face competition with respect to our current products, Galafold ® , Pombiliti ® + Opfolda ® and product candidates, and will likely face competition for any products we may seek to develop or commercialize in the future, from major pharmaceutical companies, specialty pharmaceutical companies, and biotechnology and gene therapy companies worldwide.
We face competition with respect to our current products, Galafold ® , Pombiliti ® + Opfolda ® and product candidates, including DMX-200, and will likely face competition for any products we may seek to develop or commercialize in the future, from major pharmaceutical companies, specialty pharmaceutical companies, and biotechnology and gene therapy companies worldwide.
Galafold ® and Pombiliti ® + Opfolda ® , as well as any of our product candidates that receive regulatory approval may nonetheless fail to gain sufficient market acceptance by physicians, patients, third-party payors and others in the medical community.
Galafold ® and Pombiliti ® + Opfolda ® , as well as any of our product candidates, including DMX-200, that receive regulatory approval may nonetheless fail to gain sufficient market acceptance by physicians, patients, third-party payors and others in the medical community.
We may need to obtain licenses for intellectual property rights from others and may not be able to obtain these licenses on commercially reasonable terms, if at all. -53- Table of Contents We are currently, and may become, involved in Hatch-Waxman litigation to protect or enforce our patents or other intellectual property, which could be expensive, time consuming, and unsuccessful.
We may need to obtain licenses for intellectual property rights from others and may not be able to obtain these licenses on commercially reasonable terms, if at all. -56- Table of Contents We may become involved in Hatch-Waxman litigation to protect or enforce our patents or other intellectual property, which could be expensive, time consuming, and unsuccessful.
Such failure could also result in product liability claims, product recalls, product seizures or withdrawals, delays or failures in testing or delivery, cost overruns or other problems that could seriously harm our business, profitability, or reputation. The FDA and regulatory authorities in other jurisdictions require our contract manufacturers to comply with cGMP regulations.
Such failure could also result in product liability claims, product recalls, product seizures or withdrawals, delays or failures in testing or delivery, cost overruns or other problems that could seriously harm our business, profitability, or reputation. -45- Table of Contents The FDA and regulatory authorities in other jurisdictions require our contract manufacturers to comply with cGMP regulations.
As of December 31, 2024, we had 499 full-time employees. As our development and commercialization strategies evolve, we will need additional managerial, operational, sales, marketing, financial, technical operations and other resources. Our management, personnel and systems currently in place may not be adequate to support this future growth.
As of December 31, 2025, we had 511 full-time employees. As our development and commercialization strategies evolve, we will need additional managerial, operational, sales, marketing, financial, technical operations and other resources. Our management, personnel and systems currently in place may not be adequate to support this future growth.
Participation in these programs and compliance with the applicable requirements may subject us to potentially significant discounts on our products, increased infrastructure costs, potential liability for the failure to report such prices in an accurate and timely manner, and potentially limit our ability to offer certain marketplace discounts; -37- Table of Contents • U.S.
Participation in these programs and compliance with the applicable requirements may subject us to potentially significant discounts on our products, increased infrastructure costs, potential liability for the failure to report such prices in an accurate and timely manner, and potentially limit our ability to offer certain marketplace discounts; • U.S.
In addition to the factors discussed in this Annual Report on Form 10-K, these factors include: • the success of competitive products or technologies; • regulatory actions with respect to our products or product candidates or our competitors' products or product candidates; • actual or anticipated changes in our growth rate relative to our competitors; • the outcome of any patent infringement or other litigation that may be brought against us or we may bring against others; • announcements by us or our competitors of significant acquisitions, strategic collaborations, joint ventures, collaborations or capital commitments; • results of clinical trials of our product candidates or those of our competitors; • regulatory or legal developments in the E.U., U.K., U.S. and other countries; • developments or disputes concerning patent applications, issued patents or other proprietary rights; • the recruitment or departure of key personnel; • the level of expenses related to our product or any of our product candidates or clinical development programs; • actual or anticipated variations in our quarterly operating results; • the number and characteristics of our efforts to in-license or acquire additional product candidates or products; • introduction of new products or services by us or our competitors; • failure to meet the estimates and projections of the investment community or that we may otherwise provide to the public; • actual or anticipated changes in estimates as to financial results, development timelines or recommendations by securities analysts; • variations in our financial results or those of companies that are perceived to be similar to us; • fluctuations in the valuation of companies perceived by investors to be comparable to us; • share price and volume fluctuations attributable to inconsistent trading volume levels of our shares; • announcement or expectation of additional financing efforts; • sales of our common stock by us, our insiders or our other stockholders; • changes in accounting practices; • lawsuits and other claims asserted against us; • changes in the structure of healthcare payment systems; • market conditions in the pharmaceutical and biotechnology sectors; • general economic, industry and market conditions; • publication of research reports about us, our competitors or our industry, or positive or negative recommendations or withdrawal of research coverage by securities or industry analysts; • other events or factors, many of which are beyond our control; and • the other factors described in this "Risk Factors" section. -64- Table of Contents In addition, the stock market in general, and pharmaceutical and biotechnology companies in particular, have experienced extreme price and volume fluctuations that have often been unrelated or disproportionate to the operating performance of these companies.
In addition to the factors discussed in this Annual Report on Form 10-K, these factors include: • the perceived likelihood of the completion of the pending transaction with BioMarin; • the success of competitive products or technologies; • regulatory actions with respect to our products or product candidates or our competitors' products or product candidates; • actual or anticipated changes in our growth rate relative to our competitors; • the outcome of any patent infringement or other litigation that may be brought against us or we may bring against others; • announcements by us or our competitors of significant acquisitions, mergers, strategic collaborations, joint ventures, collaborations or capital commitments; • results of clinical trials of our product candidates or those of our competitors; • regulatory or legal developments in the E.U., U.K., U.S. and other countries; • developments or disputes concerning patent applications, issued patents or other proprietary rights; • the recruitment or departure of key personnel; • the level of expenses related to our product or any of our product candidates or clinical development programs; • actual or anticipated variations in our quarterly operating results; • the number and characteristics of our efforts to in-license or acquire additional product candidates or products; • introduction of new products or services by us or our competitors; • failure to meet the estimates and projections of the investment community or that we may otherwise provide to the public; • actual or anticipated changes in estimates as to financial results, development timelines or recommendations by securities analysts; • variations in our financial results or those of companies that are perceived to be similar to us; • fluctuations in the valuation of companies perceived by investors to be comparable to us; • share price and volume fluctuations attributable to inconsistent trading volume levels of our shares; • announcement or expectation of additional financing efforts; • sales of our common stock by us, our insiders or our other stockholders; • changes in accounting practices; • lawsuits and other claims asserted against us; • changes in the structure of healthcare payment systems; • market conditions in the pharmaceutical and biotechnology sectors; • general economic, industry and market conditions; • publication of research reports about us, our competitors or our industry, or positive or negative recommendations or withdrawal of research coverage by securities or industry analysts; -67- Table of Contents • other events or factors, many of which are beyond our control; and • the other factors described in this "Risk Factors" section.
We may also face additional manufacturing and supply-chain risks due to the regulatory and political structure of the PRC, or as a result of the international relationship between the PRC and the U.S., including but not limited to potential new regulations and/or sanctions imposed by the U.S. government on the PRC or WuXi specifically, such as the contemplated BIOSECURE Act which, in its current form, would prohibit entities that receive federal funds from using biotechnology that is from a company associated with a foreign adversary, or any of the other countries in which our products are marketed.
We may also face additional manufacturing and supply-chain risks due to the regulatory and political structure of the PRC, or as a result of the international relationship between the PRC and the U.S., including but not limited to potential new regulations and/or sanctions imposed by the U.S. government on the PRC or WuXi specifically, such as the BIOSECURE Act which prohibits entities that receive federal funds from using biotechnology that is from a company associated with a foreign adversary, or any of the other countries in which our products are marketed.
Complying with such changes could be costly, and a failure to comply in a timely manner could lead to fines, penalties, or the inability to commercialize such products in those jurisdictions, materially impacting our revenue, cash flow, and financial guidance targets. -45- Table of Contents As noted above, we currently rely on WuXi, as the sole supplier of our biologic product, Pombiliti ® .
Complying with such changes could be costly, and a failure to comply in a timely manner could lead to fines, penalties, or the inability to commercialize such products in those jurisdictions, materially impacting our revenue, cash flow, and financial guidance targets. As noted above, we currently rely on WuXi, as the primary supplier of our biologic product, Pombiliti ® .
Our ability to use our net operating loss carryforwards and certain other tax attributes may be limited. As of December 31, 2024, we had U.S. federal and state net operating loss carry forwards ("NOLs") of approximately $1.1 billion and $1.0 billion, respectively. The federal carry forward for losses generated prior to 2018 will expire in 2031 through 2037.
Our ability to use our net operating loss carryforwards and certain other tax attributes may be limited. As of December 31, 2025, we had U.S. federal and state net operating loss carry forwards ("NOLs") of approximately $1.2 billion and $1.0 billion, respectively. The federal carry forward for losses generated prior to 2018 will expire in 2033 through 2037.
We expect to continue to incur significant costs in the foreseeable future as we: • continue our development and commercialization of our products and seek regulatory approvals for our product candidates in the U.S., E.U., U.K., Japan and other foreign countries, as applicable; • conduct additional clinical trials to support the full approval of Galafold ® in the U.S. and post-approval commitments or trials in the E.U. and other geographies; -46- Table of Contents • continue communicating with the EMA, as necessary, regarding post-marketing requirements and clinical trials for Galafold ® ; • continue to or initiate the regulatory submission process for marketing approval of Galafold ® and Pombiliti ® + Opfolda ® outside of the U.S. and E.U. and other foreign jurisdictions where approved, as applicable; • build and maintain our commercial infrastructure so that it is capable of supporting product sales, marketing and distribution of Galafold ® and Pombiliti ® + Opfolda ® , as well as our other product candidates in Europe, Japan, the U.S., or other territories in which we have received or may receive regulatory approval; • continue our next-generation product research; and • continue our rigorous prosecution and defense of our patent portfolio.
We expect to continue to incur significant costs in the foreseeable future as we: • continue our development and commercialization of our products and seek regulatory approvals for our product candidates in the U.S., E.U., U.K., Japan and other foreign countries, as applicable; -49- Table of Contents • conduct additional clinical trials to support the full approval of Galafold ® in the U.S. and post-approval commitments or trials in the E.U. and other geographies; • continue communicating with the EMA, as necessary, regarding post-marketing requirements and clinical trials for Galafold ® ; • continue to or initiate the regulatory submission process for marketing approval of Galafold ® and Pombiliti ® + Opfolda ® outside of the U.S. and E.U. and other foreign jurisdictions where approved, as applicable; • build and maintain our commercial infrastructure so that it is capable of supporting product sales, marketing and distribution of Galafold ® and Pombiliti ® + Opfolda ® , as well as our other product candidates in Europe, Japan, the U.S., or other territories in which we have received or may receive regulatory approval; • continue our next-generation product research; • prepare for the U.S. commercial launch of DMX-200, should it be approved by the FDA; and • continue our rigorous prosecution and defense of our patent portfolio.
Federal net operating losses incurred in 2018 and onward have an indefinite expiration under the Tax Act. Most of the state net operating loss carry forwards generated prior to 2009 have expired through 2016. The remaining state net operating loss carry forwards including those generated in 2009 through 2024 will expire in 2028 through 2042.
Federal net operating losses incurred in 2018 and onward have an indefinite expiration under the Tax Act. Most of the state net operating loss carry forwards generated prior to 2009 have expired through 2016. The remaining state net operating loss carry forwards including those generated in 2009 through 2025 will expire in 2028 through 2045.
Failure to obtain regulatory approval for our products and product candidates will prevent us from commercializing our products in jurisdictions beyond those in which we have obtained regulatory approval for our product or in any jurisdictions for our product candidates.
Failure to obtain regulatory approval for our products and product candidates, including DMX-200, will prevent us from commercializing our products in jurisdictions beyond those in which we have obtained regulatory approval for our product or in any jurisdictions for our product candidates.
We may experience numerous unforeseen events during, or as a result of, clinical trials that could delay or prevent our ability to receive regulatory approval or commercialize our product candidates, including: • clinical trials of our product candidates may produce negative or inconclusive results, and we may decide, or regulators may require us, to conduct additional clinical trials or abandon product development programs; • the number of patients required for clinical trials of our product candidates may be larger than we anticipate, enrollment in these clinical trials may be slower than we anticipate, or patients may drop out of these clinical trials at a higher rate than we anticipate; • we may be unable to enroll a sufficient number of patients in our trials to ensure adequate statistical power to detect any statistically significant treatment effects; • our third-party contractors may fail to comply with regulatory requirements or meet their contractual obligations to us in a timely manner, or at all; • regulators, institutional review boards, or independent ethics committees may not authorize us or our investigators to commence a clinical trial or conduct a clinical trial at a prospective trial site; • we may have delays in reaching or fail to reach agreement on acceptable clinical trial contracts or clinical trial protocols with prospective trial sites; • we may have to suspend or terminate clinical trials of our product candidates for various reasons, including a finding that the participants are being exposed to unacceptable health risks; • regulators, institutional review boards, or independent ethics committees may require that we or our investigators suspend or terminate clinical research for various reasons, including noncompliance with regulatory requirements or a finding that the participants are being exposed to unacceptable health risks; • the cost of clinical trials of our product candidates may be greater than we anticipate; • the supply or quality of our product candidates or other materials necessary to conduct clinical trials of our product candidates may be insufficient or inadequate; or • our product candidates may have undesirable side effects or other unexpected characteristics, causing us or our investigators, regulators, institutional review boards or independent ethics committees to suspend or terminate the trials.
We may experience numerous unforeseen events during, or as a result of, clinical trials that could delay or prevent our ability to receive regulatory approval or commercialize our product candidates, including: • clinical trials of our product candidates may produce negative or inconclusive results, and we may decide, or regulators may require us, to conduct additional clinical trials or abandon product development programs; • the number of patients required for clinical trials of our product candidates may be larger than we anticipate, enrollment in these clinical trials may be slower than we anticipate, or patients may drop out of these clinical trials at a higher rate than we anticipate; • we may be unable to enroll a sufficient number of patients in our trials to ensure adequate statistical power to detect any statistically significant treatment effects; • our third-party contractors may fail to comply with regulatory requirements or meet their contractual obligations to us in a timely manner, or at all; • regulators, institutional review boards, or independent ethics committees may not authorize us or our investigators to commence a clinical trial or conduct a clinical trial at a prospective trial site; • we may have delays in reaching or fail to reach agreement on acceptable clinical trial contracts or clinical trial protocols with prospective trial sites; • we may have to suspend or terminate clinical trials of our product candidates for various reasons, including a finding that the participants are being exposed to unacceptable health risks; • regulators, institutional review boards, or independent ethics committees may require that we or our investigators suspend or terminate clinical research for various reasons, including noncompliance with regulatory requirements or a finding that the participants are being exposed to unacceptable health risks; • the cost of clinical trials of our product candidates may be greater than we anticipate; • the supply or quality of our product candidates or other materials necessary to conduct clinical trials of our product candidates may be insufficient or inadequate; • our product candidates may have undesirable side effects or other unexpected characteristics, causing us or our investigators, regulators, institutional review boards or independent ethics committees to suspend or terminate the trials; or -42- Table of Contents • we may in-license product candidates and, by the terms of such licenses, need to rely on third parties to conduct certain clinical trials that may be designed, powered or otherwise conducted in a manner over which we may not have absolute control.
Reimbursement may impact the demand for, or the price of, Galafold ® , Pombiliti ® + Opfolda ® , or any product candidate for which we obtain marketing approval.
Reimbursement may impact the demand for, or the price of, Galafold ® , Pombiliti ® + Opfolda ® , or any product candidate, including DMX-200, for which we obtain marketing approval.
Obtaining approval for all of our product candidates, whether those currently in our pipeline or those we acquire or in-license in the future, is highly uncertain and we may fail to obtain regulatory approval in any or all jurisdictions.
Obtaining approval for all of our product candidates, whether those currently in our pipeline, such as DMX-200, or those we acquire or in-license in the future, is highly uncertain and we may fail to obtain regulatory approval in any or all applicable jurisdictions.
Our ability to generate revenue from our current or future products and product candidates depends on a number of factors, including our ability to: • successfully complete development activities and obtain additional regulatory, pricing, and reimbursement approvals for, and continue to successfully commercialize, Galafold ® and Pombiliti ® + Opfolda ® ; • complete regulatory submissions and obtain regulatory approval in target geographies for Pombiliti ® + Opfolda ® ; • develop and maintain a commercial organization capable of sales, marketing, and distribution for Galafold ®, Pombiliti ® + Opfolda ® , and any product candidates we intend to market if approved, in the countries where we have chosen to commercialize the products ourselves, including the U.S., E.U., U.K., and Japan; • manufacture commercial quantities of our products at acceptable cost levels; • obtain a commercially viable price for our products; • obtain coverage and adequate reimbursement from third parties, including government payors; • successfully satisfy post-marketing requirements that the FDA, EMA, or other foreign regulatory authorities may impose for Galafold ® , Pombiliti ® + Opfolda ® , or any of our other product candidates that may receive regulatory approval, including pediatric trials and patient registries; • successfully develop or acquire new products and product candidates; • successfully complete development activities, including the necessary pre-clinical studies and clinical trials, with respect to product candidates; • successfully protect our intellectual property rights; and • successfully navigate the evolving geopolitical landscape and any adverse impacts arising therefrom, including actions by governments, our customers, our suppliers or other third parties. -47- Table of Contents Even if we are able to generate significant revenues from the sale of our products and accurately predict and control expenses, we may not reach our financial guidance or become profitable and may need to obtain additional funding to continue operations.
Our ability to generate revenue from our current or future products and product candidates depends on a number of factors, including our ability to: • successfully complete development activities and obtain additional regulatory, pricing, and reimbursement approvals for, and continue to successfully commercialize, Galafold ® and Pombiliti ® + Opfolda ® ; • complete regulatory submissions and obtain regulatory approval in target geographies for Pombiliti ® + Opfolda ® ; • develop and maintain a commercial organization capable of sales, marketing, and distribution for Galafold ®, Pombiliti ® + Opfolda ® , and any product candidates we intend to market if approved, in the countries where we have chosen to commercialize the products ourselves, including the U.S., E.U., U.K., and Japan; • manufacture commercial quantities of our products at acceptable cost levels; • obtain a commercially viable price for our products; • obtain coverage and adequate reimbursement from third parties, including government payors; • successfully satisfy post-marketing requirements that the FDA, EMA, or other foreign regulatory authorities may impose for Galafold ® , Pombiliti ® + Opfolda ® , or any of our other product candidates that may receive regulatory approval, including pediatric trials and patient registries; • successfully develop or acquire new products and product candidates; • successfully complete development activities, including the necessary pre-clinical studies and clinical trials, with respect to product candidates; • successfully protect our intellectual property rights; and -50- Table of Contents • successfully navigate the evolving geopolitical landscape and any adverse impacts arising therefrom, including actions by governments, our customers, our suppliers or other third parties.
These regulations cover all aspects of the manufacturing, testing, quality control and recordkeeping relating to our product candidates and any products that we may commercialize, including Galafold ® , Pombiliti ® + Opfolda ® , and our gene therapy product candidates.
These regulations cover all aspects of the manufacturing, testing, quality control and recordkeeping relating to our product candidates and any products that we may commercialize, including Galafold ® , Pombiliti ® + Opfolda ® , and DMX-200, if approved.
If we are found to have promoted off-label uses, we may become subject to significant liability. The FDA and other regulatory agencies strictly regulate the promotional claims that may be made about prescription drug products.
The FDA and other regulatory agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses. If we are found to have promoted off-label uses, we may become subject to significant liability. The FDA and other regulatory agencies strictly regulate the promotional claims that may be made about prescription drug products.
If our common stock is delisted by NASDAQ, we could face significant material adverse consequences, including: • a limited availability of market quotations for our securities; • reduced liquidity with respect to our securities; • a determination that our shares are a "penny stock," which will require brokers trading in our shares to adhere to more stringent rules, possibly resulting in a reduced level of trading activity in the secondary trading market for our shares; • a limited amount of news and analyst coverage for our company; and -65- Table of Contents • a decreased ability to issue additional securities or obtain additional financing in the future.
If our common stock is delisted by NASDAQ, we could face significant material adverse consequences, including: • a limited availability of market quotations for our securities; • reduced liquidity with respect to our securities; • a determination that our shares are a "penny stock," which will require brokers trading in our shares to adhere to more stringent rules, possibly resulting in a reduced level of trading activity in the secondary trading market for our shares; • a limited amount of news and analyst coverage for our company; and • a decreased ability to issue additional securities or obtain additional financing in the future. -68- Table of Contents If securities or industry analysts do not publish research or reports or publish unfavorable research about our business, the price of our common stock and trading volume could decline.
Further, the success of Our Commercial Products will depend on a number of factors, including the following: • obtaining a sufficiently broad label in each territory that would not unduly restrict patient access; • obtaining additional foreign approvals for Our Commercial Products; • continuing to build and maintain an infrastructure capable of supporting product sales, marketing, and distribution of Our Commercial Products in the U.S., Europe, Japan and other territories where we pursue commercialization directly; • maintaining commercial manufacturing arrangements with third-party manufacturers; • maintaining commercial distribution agreements with third-party distributors; • launching commercial sales of Our Commercial Products, where approved, whether alone or in collaboration with others; • obtaining acceptance of Our Commercial Products, where approved, by patients, the medical community, and third-party payors; -25- Table of Contents • competing effectively with other therapies, including competitor products, potential generics and gene therapies; • identifying new patients who could benefit from Our Commercial Products successfully; • continuing an acceptable safety profile of Our Commercial Products; • obtaining and maintaining patent and trade secret protection and regulatory exclusivity; • protecting and enforcing our rights in our intellectual property portfolio; and • obtaining and maintaining a commercially viable price.
Further, the success of Our Commercial Products will depend on a number of factors, including the following: • obtaining a sufficiently broad label in each territory that would not unduly restrict patient access; • obtaining additional foreign approvals for Our Commercial Products; • continuing to build and maintain an infrastructure capable of supporting product sales, marketing, and distribution of Our Commercial Products in the U.S., Europe, Japan and other territories where we pursue commercialization directly; • maintaining commercial manufacturing arrangements with third-party manufacturers; • maintaining commercial distribution agreements with third-party distributors; • launching commercial sales of Our Commercial Products, where approved, whether alone or in collaboration with others; • obtaining acceptance of Our Commercial Products, where approved, by patients, the medical community, and third-party payors; • competing effectively with other therapies, including competitor products, potential generics and gene therapies; • identifying new patients who could benefit from Our Commercial Products successfully; • continuing an acceptable safety profile of Our Commercial Products; • obtaining and maintaining patent and trade secret protection and regulatory exclusivity; • protecting and enforcing our rights in our intellectual property portfolio; and • obtaining and maintaining a commercially viable price. -28- Table of Contents If we do not achieve one or more of these factors in a timely manner or at all, we could experience significant delays or an inability to successfully commercialize Our Commercial Products, which would materially harm our business and ability to meet our financial goals and debt covenants.
We may seek additional capital through a combination of private and public equity offerings, debt financings, receivables or royalty financings, strategic collaborations and alliances, restructuring and licensing arrangements.
If the Merger is not consummated, we may seek additional capital through a combination of private and public equity offerings, debt financings, receivables or royalty financings, strategic collaborations and alliances, restructuring and licensing arrangements.
This could cause the market price of our common stock to drop significantly, even if our business is doing well. Sales of a substantial number of shares of our common stock in the public market could occur at any time.
A significant portion of our total outstanding shares may be sold into the market. This could cause the market price of our common stock to drop significantly, even if our business is doing well. Sales of a substantial number of shares of our common stock in the public market could occur at any time.
In addition, later discovery of previously unknown adverse events or other problems with our products, manufacturers or manufacturing processes, or failure to comply with regulatory requirements, may yield various results, including: • restrictions on such products, manufacturers, or manufacturing processes; • changes to or restrictions on the labeling or marketing of a product; • restrictions on product distribution or use; • requirements to implement a REMS; • requirements to conduct post-marketing studies or clinical trials; • warning letters, untitled letters, or Form 483s; • withdrawal of the products from the market; • refusal to approve pending applications or supplements to approved applications that we submit; • recall of products; • fines, restitution, or disgorgement of profits or revenues; • suspension or withdrawal of marketing approvals; • refusal to permit the import or export of our products; • product seizure; • injunctions; or • the imposition of civil or criminal penalties. -35- Table of Contents Non-compliance with E.U. and U.K. requirements regarding safety monitoring or pharmacovigilance, and with requirements related to the development of products for the pediatric population, can also result in significant financial penalties.
In addition, later discovery of previously unknown adverse events or other problems with our products, manufacturers or manufacturing processes, or failure to comply with regulatory requirements, may yield various results, including: • restrictions on such products, manufacturers, or manufacturing processes; -38- Table of Contents • changes to or restrictions on the labeling or marketing of a product; • restrictions on product distribution or use; • requirements to implement a REMS; • requirements to conduct post-marketing studies or clinical trials; • warning letters, untitled letters, or Form 483s; • withdrawal of the products from the market; • refusal to approve pending applications or supplements to approved applications that we submit; • recall of products; • fines, restitution, or disgorgement of profits or revenues; • suspension or withdrawal of marketing approvals; • refusal to permit the import or export of our products; • product seizure; • injunctions; or • the imposition of civil or criminal penalties.
We are currently working with WuXi to develop a second manufacturing facility for Pombiliti ® in Dundalk, Ireland. This facility will require substantial time and investment to ensure it meets applicable regulatory standards governing the manufacture of commercial pharmaceutical products. This facility may experience delays in getting approved or require an additional outlay of capital.
We are currently working with WuXi to develop a second manufacturing facility for Pombiliti ® in Dundalk, Ireland. This facility will require substantial time and investment to ensure it meets applicable regulatory standards governing the manufacture of commercial pharmaceutical products.
As of the end of 2022, we received Paragraph 4 certifications from three ANDA filers for Galafold ® and initiated Hatch-Waxman litigation against these ANDA filers. In the fourth quarter of 2024, we settled the litigation with one of the ANDA filers, but the litigation against the others remains pending.
At the end of 2022, we received Paragraph 4 certifications from three ANDA filers for Galafold ® and initiated Hatch-Waxman litigation against these ANDA filers. In the fourth quarter of 2024, we settled the litigation with one of the ANDA filers, and in the fourth quarter of 2025 we settled the litigation with the remaining filers.
Our executive officers, directors and principal stockholders maintain the ability to exert significant influence and control over matters submitted to our stockholders for approval. Our executive officers, directors and principal stockholders beneficially own shares representing approximately 51% of our common stock as of December 31, 2024.
Our executive officers, directors and principal stockholders maintain the ability to exert significant influence and control over matters submitted to our stockholders for approval. Our executive officers, directors and principal stockholders beneficially own shares representing approximately 20% of our common stock as of February 12, 2026.
The market price of our common stock is highly volatile and may be subject to wide fluctuations in response to numerous factors, some of which are beyond our control.
The price of our common stock may be volatile and fluctuate substantially, which could result in substantial losses for purchasers of our common stock. The market price of our common stock is highly volatile and may be subject to wide fluctuations in response to numerous factors, some of which are beyond our control.
There also may be adverse publicity associated with litigation that could negatively affect customer perception of our business, regardless of whether the allegations are valid or whether we are ultimately found liable.
There also may be adverse publicity associated with litigation that could negatively affect customer perception of our business, regardless of whether the allegations are valid or whether we are ultimately found liable. As a result, litigation may adversely affect our business, financial condition, results of operations or liquidity.
If our estimates of the prevalence of Fabry disease, Pompe disease, or other rare diseases or of the number of patients who may benefit from treatment with our products or product candidates prove to be incorrect, or if we are unable to obtain traditional approval for Galafold ® which was granted approval in the U.S. under the accelerated approval program and/or expand the patient populations and approved indications of Galafold ® and Pombiliti ® + Opfolda ® in the jurisdictions in which they are approved, the market opportunities for our products and product candidates, if approved, may be smaller than we believe and our prospects for generating revenue at our guidance levels may be adversely affected and our business may suffer. -28- Table of Contents Galafold ® and Pombiliti ® + Opfolda ® , or any of our product candidates that receive regulatory approval, may fail to achieve the degree of market acceptance by physicians, patients, third-party payors and others in the medical community necessary for commercial success.
If our estimates of the prevalence of Fabry disease, Pompe disease, or other rare diseases or of the number of patients who may benefit from treatment with our products or product candidates prove to be incorrect, or if we are unable to obtain traditional approval for Galafold ® which was granted approval in the U.S. under the accelerated approval program and/or expand the patient populations and approved indications of Galafold ® and Pombiliti ® + Opfolda ® in the jurisdictions in which they are approved, the market opportunities for our products and product candidates, if approved, may be smaller than we believe and our prospects for generating revenue at our guidance levels may be adversely affected and our business may suffer.
If patents are not issued in respect of our pending patent applications, we may not be able to stop competitors from marketing similar products in Europe and other countries in which we do not have issued patents.
These pending applications include, among others, some of the patent applications for Pombiliti ® + Opfolda ® , and Galafold ® . If patents are not issued in respect of our pending patent applications, we may not be able to stop competitors from marketing similar products in Europe and other countries in which we do not have issued patents.
If securities or industry analysts do not initiate or continue coverage of us, the trading price for our common stock would be negatively affected. In the event we obtain securities or industry analyst coverage, if one or more of the analysts who covers us downgrades our common stock, the price of our common stock would likely decline.
In the event we obtain securities or industry analyst coverage, if one or more of the analysts who covers us downgrades our common stock, the price of our common stock would likely decline.
In addition, orphan drug exclusivity will not prevent the approval of a product that is the same drug as our product or product candidate if the FDA finds that we cannot assure the availability of sufficient quantities of the drug to meet the needs of the persons with the disease or condition for which the drug was designated. -40- Table of Contents Failure to obtain or maintain regulatory approval in foreign jurisdictions would prevent us from marketing our products abroad.
In addition, orphan drug exclusivity will not prevent the approval of a product that is the same drug as our product or product candidate if the FDA finds that we cannot assure the availability of sufficient quantities of the drug to meet the needs of the persons with the disease or condition for which the drug was designated.
The regulatory approval process outside the U.S. generally includes all of the risks associated with obtaining FDA approval. In addition, some countries outside the U.S. require approval of the sales price of a drug before it can be marketed. In many countries, separate procedures must be followed to obtain reimbursement.
The time required to obtain approval may differ from that required to obtain FDA approval. The regulatory approval process outside the U.S. generally includes all of the risks associated with obtaining FDA approval. In addition, some countries outside the U.S. require approval of the sales price of a drug before it can be marketed.
If securities or industry analysts do not publish research or reports or publish unfavorable research about our business, the price of our common stock and trading volume could decline. The trading market for our common stock depends in part on the research and reports that securities or industry analysts publish about us or our business.
The trading market for our common stock depends in part on the research and reports that securities or industry analysts publish about us or our business. If securities or industry analysts do not initiate or continue coverage of us, the trading price for our common stock would be negatively affected.
If our manufacturers or we are unable to purchase these materials for commercial distribution of our approved products, the commercial launch of our products and product candidates would be delayed or there would be a shortage in supply, which would materially affect our ability to generate revenues from the sale of our products or product candidates.
If our manufacturers or we are unable to purchase these materials for commercial distribution of our approved products, the commercial launch of our products and product candidates would be delayed or there would be a shortage in supply, which would materially affect our ability to generate revenues from the sale of our products or product candidates. -48- Table of Contents Manufacturing issues may arise that could increase product and regulatory approval costs or delay commercialization.
We may not be able to initiate or continue clinical trials for our product candidates if we are unable to locate and enroll a sufficient number of eligible patients to participate in these trials.
If we experience delays or difficulties in the enrollment of patients in our clinical trials, our receipt of necessary regulatory approvals could be delayed or prevented. We may not be able to initiate or continue clinical trials for our product candidates if we are unable to locate and enroll a sufficient number of eligible patients to participate in these trials.
In order to market and sell our products in Europe and many other jurisdictions, we must obtain separate marketing approvals and comply with numerous and varying regulatory requirements. The approval procedure varies among countries and can involve additional testing. The time required to obtain approval may differ from that required to obtain FDA approval.
Failure to obtain or maintain regulatory approval in foreign jurisdictions would prevent us from marketing our products abroad. In order to market and sell our products in Europe and many other jurisdictions, we must obtain separate marketing approvals and comply with numerous and varying regulatory requirements. The approval procedure varies among countries and can involve additional testing.
Significant preclinical study or clinical trial delays also could shorten any periods during which we may have the exclusive right to commercialize our product candidates, allow our competitors to bring products to market before we do, or impair our ability to successfully commercialize our product candidates, and so may harm our business and results of operations. -39- Table of Contents If we experience delays or difficulties in the enrollment of patients in our clinical trials, our receipt of necessary regulatory approvals could be delayed or prevented.
Significant preclinical study or clinical trial delays also could shorten any periods during which we may have the exclusive right to commercialize our product candidates, allow our competitors to bring products to market before we do, or impair our ability to successfully commercialize our product candidates, and so may harm our business and results of operations.
As a result, litigation may adversely affect our business, financial condition, results of operations or liquidity. -66- Table of Contents We may be exposed to employment-related claims and losses which could have an adverse effect on our business. As we continue to increase the size of our workforce, the risk of potential employment-related claims will also increase.
We may be exposed to employment-related claims and losses which could have an adverse effect on our business. -69- Table of Contents As we continue to increase the size of our workforce, the risk of potential employment-related claims will also increase.
Our current and anticipated future dependence upon others for the manufacture of our product candidates may adversely affect our future profit margins, our ability to meet our obligations under our credit facility, and our ability to develop product candidates and commercialize any products that receive regulatory approval on a timely and competitive basis. -42- Table of Contents We rely on third parties to distribute our products, and those third parties may not perform satisfactorily, including failing to deliver products to meet demand.
Our current and anticipated future dependence upon others for the manufacture of our product candidates may adversely affect our future profit margins, our ability to meet our obligations under our credit facility, and our ability to develop product candidates and commercialize any products that receive regulatory approval on a timely and competitive basis.
A successful product liability claim or a series of claims brought against us could cause our stock price to fall and, if judgments exceed our insurance coverage, could decrease our available cash and adversely affect our business including our ability to service our debt and comply with the liquidity and revenue covenants contained therein.
A successful product liability claim or a series of claims brought against us could cause our stock price to fall and, if judgments exceed our insurance coverage, could decrease our available cash and adversely affect our business including our ability to service our debt and comply with the liquidity and revenue covenants contained therein. -36- Table of Contents If the FDA or other applicable regulatory authorities approve generic or biosimilar products that compete with our products or any of our product candidates, it could reduce sales of our products or product candidates.
Our business may be impacted by actions of the new U.S. administration, including Executive Orders, policies, new legislation, and judicial decisions The impact of the new U.S. administration is currently unknown. However, actions of the administration may cause us to change our business operations, with an unknown impact to our stakeholders, including patients, healthcare providers, and employees.
Our business may be impacted by actions of the U.S. government, including Executive Orders, policies, new legislation, and judicial decisions Actions by the U.S. government may require us to change our business operations, resulting in unknown and unforeseeable impacts to our stakeholders, including patients, healthcare providers, and employees.

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Item 1C. Cybersecurity

Cybersecurity — threats and controls disclosure

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Biggest changeTechnical Safeguards: The Company deploys technical safeguards that are designed to protect the Company’s information systems from cybersecurity threats, including firewalls, intrusion prevention and detection systems, anti-malware functionality and access controls, 24x7 security monitoring, and other controls which are evaluated and improved through vulnerability assessments and cybersecurity threat intelligence. • Incident Response and Recovery Planning: The Company has established and maintains systematic incident response and recovery plans that address the Company’s response to a cybersecurity incident, and such plans are tested and evaluated on a periodic basis. • Third-Party Risk Management: The Company maintains a systematic, risk-based approach to identifying and overseeing cybersecurity risks presented by third parties, including vendors, service providers and other external users -67- Table of Contents of the Company’s systems, as well as the systems of third parties that could adversely impact our business in the event of a cybersecurity incident affecting those third-party systems. • Education and Awareness: The Company provides regular, mandatory cybersecurity training for all personnel as a means to equip the Company’s workforce with effective tools to recognize, address and communicate potential or actual threats to the Company’s cybersecurity systems.
Biggest changeTechnical Safeguards: The Company deploys technical safeguards that are designed to protect the Company’s information systems from cybersecurity threats, including firewalls, intrusion prevention and detection systems, anti-malware functionality and access controls, 24x7 security monitoring, and other controls which are evaluated and improved through vulnerability assessments and cybersecurity threat intelligence. • Incident Response and Recovery Planning: The Company has established and maintains systematic incident response and recovery plans that address the Company’s response to a cybersecurity incident, and such plans are tested and evaluated on a periodic basis. • Third-Party Risk Management: The Company maintains a systematic, risk-based approach to identifying and overseeing cybersecurity risks presented by third parties, including vendors, service providers and other external users of the Company’s systems, as well as the systems of third parties that could adversely impact our business in the event of a cybersecurity incident affecting those third-party systems. -70- Table of Contents • Education and Awareness: The Company provides regular, mandatory cybersecurity training for all personnel as a means to equip the Company’s workforce with effective tools to recognize, address and communicate potential or actual threats to the Company’s cybersecurity systems.
The CIO has served in various leadership roles in information technology and information security for over 24 years, including serving as the vice president of information technology, with direct responsibility over the cyber security program, for a large publicly-traded company and as the chief information security officer of several large healthcare organizations.
The CIO has served in various leadership roles in information technology and information security for over 25 years, including serving as the vice president of information technology, with direct responsibility over the cyber security program, for a large publicly-traded company and as the chief information security officer of several large healthcare organizations.
The CIO holds a Certified Information Systems Security Professional certification, an undergraduate degree in engineering, an MBA and a PhD in engineering. -68- Table of Contents
The CIO holds a Certified Information Systems Security Professional certification, an undergraduate degree in engineering, an MBA and a PhD in engineering. -71- Table of Contents

Item 2. Properties

Properties — owned and leased real estate

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Biggest changeItem 2. PROPERTIES The following table contains information about our current significant leased properties as of December 31, 2024.
Biggest changeItem 2. PROPERTIES The following table contains information about our current significant leased properties as of December 31, 2025.

Item 3. Legal Proceedings

Legal Proceedings — active lawsuits and investigations

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Biggest changeItem 3. LEGAL PROCEEDINGS The information called for by this item is incorporated herein by reference to the information set forth in Note 15 “Legal Proceedings” of the Notes to Consolidated Financial Statements included in Item 8 of this Report. Item 4. MINE SAFETY DISCLOSURES None. -69- Table of Contents PART II
Biggest changeItem 3. LEGAL PROCEEDINGS The information called for by this item is incorporated herein by reference to the information set forth in " -— Note 16. Legal Proceedings” in the Notes to Consolidated Financial Statements included in Item 8 of this Report. Item 4. MINE SAFETY DISCLOSURES None. -72- Table of Contents PART II

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

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Biggest changeThe stockholder return shown on the graph below is not necessarily indicative of future performance, and we do not make or endorse any predictions as to future stockholder returns. 12/31/2019 12/31/2020 12/31/2021 12/31/2022 12/31/2023 12/31/2024 Amicus Therapeutics, Inc. $100 $237 $119 $122 $146 $97 NASDAQ Composite $100 $144 $174 $116 $165 $215 NASDAQ Biotechnology $100 $126 $125 $110 $118 $114 The stock price performance included in this graph is not necessarily indicative of future stock price performance.
Biggest changeThe stockholder return shown on the graph below is not necessarily indicative of future performance, and we do not make or endorse any predictions as to future stockholder returns. 12/31/2020 12/31/2021 12/31/2022 12/31/2023 12/31/2024 12/31/2025 Amicus Therapeutics, Inc. $100 $50 $52 $62 $41 $62 NASDAQ Composite $100 $121 $81 $115 $150 $180 NASDAQ Biotechnology $100 $99 $88 $94 $91 $120 The stock price performance included in this graph is not necessarily indicative of future stock price performance.
Recent Sales of Unregistered Securities None. -70- Table of Contents Performance Graph The following performance graph compares the cumulative total return on our common stock during the last five fiscal years with the NASDAQ Composite Index (U.S.) and the NASDAQ Biotechnology Index during the same period.
Recent Sales of Unregistered Securities None. -73- Table of Contents Performance Graph The following performance graph compares the cumulative total return on our common stock during the last five fiscal years with the NASDAQ Composite Index (U.S.) and the NASDAQ Biotechnology Index during the same period.
The closing price for our common stock as reported by the NASDAQ Global Market on February 10, 2025 was $9.64 per share. As of February 10, 2025, there were 14 holders of record of our common stock. Dividends We have never declared or paid any dividends on our capital stock.
The closing price for our common stock as reported by the NASDAQ Global Market on February 12, 2026 was $14.33 per share. As of February 12, 2026, there were 15 holders of record of our common stock. Dividends We have never declared or paid any dividends on our capital stock.
Issuer Purchases of Equity Securities The following table provides certain information with respect to purchase of our common stock during the three months ended December 31, 2024: Period Total Number of Shares Purchased (1) Average Price Paid per Share Total Number of Shares Purchased as Part of Publicly Announced Plans or Programs Maximum Number (or Approximate Dollar Value) of Shares That May Yet Be Purchased Under the Plans or Programs October 1, 2024 through October 31, 2024 39,319 $ 10.38 — — November 1, 2024 through November 30, 2024 20,565 $ 10.62 — — December 1, 2024 through December 31, 2024 20,447 $ 9.36 — — Total 80,331 $ 10.18 — — ______________________________ (1) Represents shares of common stock withheld to satisfy taxes associated with the vesting of restricted stock awards.
Issuer Purchases of Equity Securities The following table provides certain information with respect to purchase of our common stock during the three months ended December 31, 2025: Period Total Number of Shares Purchased (1) Average Price Paid per Share Total Number of Shares Purchased as Part of Publicly Announced Plans or Programs Maximum Number (or Approximate Dollar Value) of Shares That May Yet Be Purchased Under the Plans or Programs October 1, 2025 through October 31, 2025 20,767 $ 8.35 — — November 1, 2025 through November 30, 2025 23,325 $ 9.28 — — December 1, 2025 through December 31, 2025 298,936 $ 13.82 — — Total 343,028 $ 13.18 — — ______________________________ (1) Represents shares of common stock withheld to satisfy taxes associated with the vesting of restricted stock awards.

Item 7. Management's Discussion & Analysis

Management's Discussion & Analysis (MD&A) — revenue / margin commentary

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Biggest changeYear Ended December 31, 2024 Compared to Year Ended December 31, 2023 The following table provides selected financial information of our operations: Years ended December 31, (in thousands) 2024 2023 Change Net product sales $ 528,295 $ 399,356 $ 128,939 Cost of goods sold 52,943 37,326 15,617 Cost of goods sold as a percentage of net product sales 10.0 % 9.3 % 0.7 % Operating expenses: Research and development 109,362 152,381 (43,019) Selling, general, and administrative 323,379 275,270 48,109 Changes in fair value of contingent consideration payable — 2,583 (2,583) Loss on impairment of assets — 1,134 (1,134) Restructuring charges 9,188 — 9,188 Depreciation and amortization 8,547 7,873 674 Other (expense) income: Interest income 5,407 7,078 (1,671) Interest expense (49,598) (50,149) 551 Loss on extinguishment of debt — (13,933) 13,933 Other expense (9,441) (15,886) 6,445 Income tax expense (27,350) (1,483) (25,867) Net loss attributable to common stockholders $ (56,106) $ (151,584) $ 95,478 Net Product Sales.
Biggest changeYear Ended December 31, 2025 Compared to Year Ended December 31, 2024 The following table provides selected financial information of our operations: Years ended December 31, (in thousands) 2025 2024 Change Net product sales $ 634,210 $ 528,295 $ 105,915 Cost of goods sold 72,929 52,943 19,986 Gross Profit 561,281 475,352 85,929 Operating expenses: Research and development 135,843 109,362 26,481 Selling, general, and administrative 383,487 323,379 60,108 Loss on impairment of assets 1,702 — 1,702 Restructuring charges — 9,188 (9,188) Depreciation and amortization 7,460 8,547 (1,087) Other (expense) income: Interest income 3,317 5,407 (2,090) Interest expense (46,159) (49,598) 3,439 Other expense 10,244 (9,441) 19,685 Income tax expense (27,301) (27,350) 49 Net loss attributable to common stockholders $ (27,110) $ (56,106) $ 28,996 Net Product Sales.
The change in operating assets was primarily due to an increase in inventory of $73.7 million to support our continued commercial growth, an increase in accounts receivable of $19.5 million, and a decrease in accounts payable and accrued expenses of $16.5 million associated with timing of payments, partially offset by an decrease in prepaid expenses and other current assets by $14.0 million.
The change in operating assets was primarily due to an increase in inventory of $73.7 million to support our continued commercial growth, an increase in accounts receivable of $19.5 million, and a decrease in accounts payable and accrued expenses of $16.5 million associated with timing of payments, partially offset by a decrease in prepaid expenses and other current assets by $14.0 million.
Our tax liabilities are largely dependent on the mix of pre-tax earnings among the many jurisdictions in which we operate and differences in the timing of the recognition of such earnings under the relevant accounting standards and tax rules. -74- Table of Contents Critical Accounting Policies and Significant Judgments and Estimates The discussion and analysis of our financial condition and results of operations are based on our financial statements, which we have prepared in accordance with U.S. generally accepted accounting principles ("U.S.
Our tax liabilities are largely dependent on the mix of pre-tax earnings among the many jurisdictions in which we operate and differences in the timing of the recognition of such earnings under the relevant accounting standards and tax rules. -77- Table of Contents Critical Accounting Policies and Significant Judgments and Estimates The discussion and analysis of our financial condition and results of operations are based on our financial statements, which we have prepared in accordance with U.S. generally accepted accounting principles ("U.S.
Discussions of 2022 items and year-to-year comparisons between 2023 and 2022 that are not included in this Form 10-K can be found in Part II, Item 7 of the Company’s Annual Report on Form 10-K for the fiscal year ended December 31, 2023, which comparisons are hereby incorporated by reference.
Discussions of 2023 items and year-to-year comparisons between 2024 and 2023 that are not included in this Form 10-K can be found in Part II, Item 7 of the Company’s Annual Report on Form 10-K for the fiscal year ended December 31, 2024, which comparisons are hereby incorporated by reference.
Our future capital requirements will depend on a number of factors, including: • the scope, progress, results and costs of clinical trials for our drug candidates; • the cost of manufacturing drug supply for our commercial, clinical and preclinical studies, including the cost of manufacturing Pombiliti ® (also referred to as "ATB200" or "cipaglucosidase alfa"); • the future results of preclinical research and subsequent clinical trials for pipeline candidates we may identify from time to time, including our ability to obtain regulatory approvals and commercialize such therapies; • the costs, timing, and outcome of regulatory review of our product candidates; • any changes in regulatory standards relating to the review of our product candidates; • any changes in laws, rules or regulations affecting our ability to manufacture, transport, test, develop, or commercialize our products, including Galafold ® , Pombiliti ® + Opfolda ® , or our product candidates; • the costs of commercialization activities, including product marketing, sales, and distribution; • the emergence of competing technologies and other adverse market developments; • the estimates regarding the potential market opportunity for our products and product candidates; • our ability to successfully commercialize Galafold ® (also referred to as "migalastat HCl"); • our ability to successfully commercialize Pombiliti ® + Opfolda ® (together, also referred to as "AT-GAA") in the E.U., U.K., and U.S., and elsewhere, if regulatory applications are approved; • our ability to manufacture or supply sufficient clinical or commercial products, including Galafold ® and Pombiliti ® + Opfolda ® ; • our ability to obtain reimbursement for Galafold ® and Pombiliti ® + Opfolda ® ; • our ability to satisfy post-marketing commitments or requirements for continued regulatory approval of Galafold ® and Pombiliti ® + Opfolda ® ; • our ability to obtain market acceptance of Galafold ® and Pombiliti ® + Opfolda ® or any other product developed or acquired that has received regulatory approval; • the costs of preparing, filing, and prosecuting patent applications and maintaining, enforcing, and defending intellectual property-related claims, including Hatch-Waxman litigation; • the impact of litigation that has been or may be brought against us or of litigation that we are pursuing or may pursue against others, including Hatch-Waxman litigation; • the extent to which we acquire or invest in businesses, products, and technologies; • our ability to successfully integrate acquired products and technologies into our business, or successfully divest or license existing products and technologies from our business, including the possibility that the expected benefits of the transactions will not be fully realized by us or may take longer to realize than expected; • our ability to establish licensing agreements, collaborations, partnerships or other similar arrangements and to obtain milestone, royalty, or other economic benefits from any such collaborators; • the costs associated with, and our ability to comply with, emerging sustainability standards, including climate reporting requirements at the local, state and national levels, especially abroad; • our ability to successfully protect our information technology systems and maintain our global operations and supply chain without interruption; • our ability to accurately forecast revenue, operating expenditures, or other metrics impacting profitability; • fluctuations in foreign currency exchange rates; and -77- Table of Contents • changes in accounting standards.
Our future capital requirements will depend on a number of factors, including: • the pending transaction with BioMarin; • the scope, progress, results and costs of clinical trials for our drug candidates; • the cost of manufacturing drug supply for our commercial, clinical and preclinical studies, including the cost of manufacturing Pombiliti ® (also referred to as "ATB200" or "cipaglucosidase alfa"); • the results of preclinical research and clinical trials for DMX-200 and other pipeline candidates we may identify from time to time, including our ability to obtain regulatory approvals and commercialize such therapies; • the costs, timing, and outcome of regulatory review of our product candidates; • any changes in regulatory standards relating to the review of our product candidates; • any changes in laws, rules or regulations, including the imposition of tariffs, most favored nation requirements, or other trade restrictions or requirements, affecting our ability to manufacture, transport, test, develop, or commercialize our products, including Galafold ® , Pombiliti ® + Opfolda ® , or our product candidates; • the costs of commercialization activities, including product marketing, sales, and distribution; • the emergence of competing technologies and other adverse market developments; • the estimates regarding the potential market opportunity for our products and product candidates; • our ability to successfully commercialize Galafold ® (also referred to as "migalastat HCl"); • our ability to successfully commercialize Pombiliti ® + Opfolda ® in the E.U., U.K., Japan, and U.S., and elsewhere, if regulatory applications are approved; • our ability to manufacture or supply sufficient clinical trial or commercial products, including DMX-200, Galafold ® and Pombiliti ® + Opfolda ® ; • our ability to obtain reimbursement for Galafold ® and Pombiliti ® + Opfolda ® ; • our ability to satisfy post-marketing commitments or requirements for continued regulatory approval of Galafold ® and Pombiliti ® + Opfolda ® ; • our ability to obtain market acceptance of Galafold ® and Pombiliti ® + Opfolda ® or any other product developed or acquired that has received regulatory approval; • the costs of preparing, filing, and prosecuting patent applications and maintaining, enforcing, and defending intellectual property-related claims, including Hatch-Waxman litigation; • the impact of litigation that has been or may be brought against us or of litigation that we are pursuing or may pursue against others, including Hatch-Waxman litigation; • the extent to which we acquire or invest in businesses, products, and technologies; • our ability to successfully integrate acquired products and technologies into our business, or successfully divest or license existing products and technologies from our business, including the possibility that the expected benefits of the transactions will not be fully realized by us or may take longer to realize than expected; • our ability to establish licensing agreements, collaborations, partnerships or other similar arrangements and to obtain milestone, royalty, or other economic benefits from any such collaborators; -80- Table of Contents • the costs associated with, and our ability to comply with, emerging sustainability standards, including climate reporting requirements at the local, state and national levels, especially abroad; • our ability to successfully protect our information technology systems and maintain our global operations and supply chain without interruption; • our ability to accurately forecast revenue, operating expenditures, or other metrics impacting profitability; • fluctuations in foreign currency exchange rates; and • changes in accounting standards.
Pombiliti ® + Opfolda ® (also referred to as "cipaglucosidase alfa-atga/miglustat") is approved in the U.S., the E.U., the U.K., and Switzerland. Multiple regulatory submissions and reimbursement processes with global health authorities are currently underway.
Pombiliti ® + Opfolda ® (also referred to as "cipaglucosidase alfa-atga/miglustat") is approved in the U.S., the E.U., the U.K., Canada, Australia, Switzerland, and Japan. Multiple regulatory submissions and reimbursement processes with global health authorities are currently underway.
Debt," to the Consolidated Financial Statements for more information. We are lessees to various operating leases for facilities and equipment. As of December 31, 2024, our undiscounted cash liabilities for operating leases were $81.0 million, with maturities ranging up through fiscal 2034. Refer to “— Note 12. Leases,” to the Consolidated Financial Statements for more information.
Debt," to the Consolidated Financial Statements for more information. We are lessees to various operating leases for facilities and equipment. As of December 31, 2025, our undiscounted cash liabilities for operating leases were $72.0 million, with maturities ranging up through fiscal 2034. Refer to “— Note 12. Leases,” to the Consolidated Financial Statements for more information.
Potential impacts of business development collaborations, pipeline expansion, and investment in manufacturing capabilities could impact our long-term capital requirements. Contractual Obligations and Commitments As of December 31, 2024, remaining maturities, including expected interest payments through maturity, on our Senior Secured Term Loan due 2029 were $548.3 million. Refer to "— Note 11.
Potential impacts of business development collaborations, pipeline expansion, and investment in manufacturing capabilities could impact our long-term capital requirements. Contractual Obligations and Commitments As of December 31, 2025, remaining maturities, including expected interest payments through maturity, on our Senior Secured Term Loan due 2029 were $498.1 million. Refer to "— Note 11.
The income tax expense for the year ended December 31, 2024 was $27.4 million. We are subject to income taxes in various jurisdictions.
The income tax expense for the year ended December 31, 2025 was $27.3 million. We are subject to income taxes in various jurisdictions.
Net Cash Used in (Provided by) Investing Activities Net cash used in investing activities for the year ended December 31, 2024 was $0.6 million. Our investing activities have consisted primarily of purchases, sales, and maturities of investments and capital expenditures.
Net Cash Used in Investing Activities Net cash used in investing activities for the year ended December 31, 2025 was $46.4 million. Our investing activities have consisted primarily of purchases, sales, and maturities of investments and capital expenditures.
Net cash used in investing activities reflects $114.8 million for the purchase of marketable securities and $3.6 million for capital expenditures, partially offset by $117.8 million for the sale and redemption of marketable securities. Net cash provided by investing activities for the year ended December 31, 2023 was $98.1 million.
Net cash used in investing activities reflects $94.4 million for the purchase of marketable securities and $3.3 million for capital expenditures, partially offset by $51.3 million for the sale and redemption of marketable securities. Net cash used in investing activities for the year ended December 31, 2024 was $0.6 million.
Although we maintain cash balances with financial institutions in excess of insured limits, we do not anticipate any losses with respect to such cash balances. For more details on the cash, cash equivalents, and marketable securities, refer to "— Note 4. Cash, Cash Equivalents, Marketable Securities, and Restricted Cash," in our Notes to Consolidated Financial Statements.
Wherever possible, we seek to minimize the potential effects of concentration and degrees of risk. Although we maintain cash balances with financial institutions in excess of insured limits, we do not anticipate any losses with respect to such cash balances. For more details on the cash, cash equivalents, and marketable securities, refer to "— Note 4.
Net Cash Provided by Financing Activities Net cash provided by financing activities for the year ended December 31, 2024 was $5.1 million.
Net Cash Provided by Financing Activities Net cash provided by financing activities for the year ended December 31, 2025 was $0.6 million.
LLC to create an at-the-market equity program ("ATM program"), pursuant to which we may offer to sell shares of our common stock having aggregate offering gross proceeds of up to $250.0 million.
LLC to create an at-the-market equity program ("ATM program"), pursuant to which we may offer to sell shares of our common stock having aggregate offering gross proceeds of up to $250.0 million. During the year ended December 31, 2025, there were no shares issued and sold through the ATM program.
Net product sales increased $128.9 million during the year ended December 31, 2024 compared to the prior year. The increase was primarily due to both the continued growth of Galafold ® in Europe and the U.S. as well as the launch of Pombiliti ® + Opfolda ® in Europe and the U.S. Cost of goods sold .
Net product sales increased $105.9 million during the year ended December 31, 2025 compared to the prior year. The increase was primarily due to both the continued growth of Galafold ® and Pombiliti ® + Opfolda ® in Europe and the U.S. and a $13.5 million favorable impact of foreign currency exchange. Cost of Goods Sold .
Our investing activities have consisted primarily of purchases, sales, and maturities of investments and capital expenditures. Net cash provided by investing activities reflects $197.2 million for the sale and redemption of marketable securities, partially offset by $91.7 million for the purchase of marketable securities and $7.4 million for capital expenditures.
Our investing activities have consisted primarily of purchases, sales, and maturities of investments and capital expenditures. Net cash used in investing activities reflects $114.8 million for the purchase of marketable securities and $3.6 million for capital expenditures, partially offset by $117.8 million for the sale and redemption of marketable securities.
As of December 31, 2024, these purchase and manufacturing obligations totaled $179.7 million, of which $102.7 million and $77.0 million are expected in 2025 and 2026, respectively. Contracts for which our commitment is variable, based on volumes, with no fixed minimum quantities, and contracts that can be canceled without payment penalties have been excluded.
Contracts for which our commitment is variable, based on volumes, with no fixed minimum quantities, and contracts that can be canceled without payment penalties have been excluded. These purchase obligations are in addition to amounts recorded on our December 31, 2025 Consolidated Balance Sheets. We have no off-balance sheet arrangements as of December 31, 2025 and 2024.
We may seek additional funding through public or private financings of debt or equity. Based on our current operating model, we believe that the current cash position, which includes expected revenues, is sufficient to fund our operations and ongoing research programs for at least the next 12 months.
Based on our current operating model and excluding any impact of the pending consummation of the Merger, we believe that the current cash position and expected revenues are sufficient to fund our operations and ongoing research programs for at least the next 12 months.
The following table summarizes our principal product development programs for each product candidate in development, and the out-of-pocket, third-party expenses incurred with respect to each product candidate: (in thousands) Years ended December 31, Projects 2024 2023 Third-party direct project expenses Galafold ® (Fabry Disease) $ 9,298 $ 12,928 Pombiliti ® + Opfolda ® (Pompe Disease) 45,215 58,826 Pre-clinical and other programs 2,437 2,553 Total third-party direct project expenses 56,950 74,307 Other project costs 1 Personnel costs 41,405 62,492 Other costs 11,007 15,582 Total other project costs 52,412 78,074 Total research and development costs $ 109,362 $ 152,381 The $43.0 million decrease in research and development costs was primarily driven by our Pombiliti ® + Opfolda ® commercial launch, decreasing both clinical spend and the number of employees supporting research and development efforts.
The following table summarizes our principal product development programs for each product candidate in development, and the out-of-pocket, third-party expenses incurred with respect to each product candidate: (in thousands) Years ended December 31, Projects 2025 2024 Third-party direct project expenses Galafold ® (Fabry Disease) $ 11,229 $ 9,298 Pombiliti ® + Opfolda ® (Pompe Disease) 48,553 45,215 DMX-200 (FSGS kidney disease) 30,000 — Pre-clinical and other programs 1,518 2,437 Total third-party direct project expenses 91,300 56,950 Other project costs 1 Personnel costs 34,373 41,405 Other costs 10,170 11,007 Total other project costs 44,543 52,412 Total research and development costs $ 135,843 $ 109,362 The $26.5 million increase in research and development costs was primarily driven by the $30.0 million upfront license payment to Dimerix.
We invest cash in excess of our immediate requirements in regard to liquidity and capital preservation in a variety of interest-bearing instruments, including obligations of U.S. government agencies and money market accounts. Wherever possible, we seek to minimize the potential effects of concentration and degrees of risk.
Cash Flow Discussion As of December 31, 2025, we had cash, cash equivalents, and marketable securities of $293.5 million. We invest cash in excess of our immediate requirements in regard to liquidity and capital preservation in a variety of interest-bearing instruments, including obligations of U.S. government agencies and money market accounts.
We used proceeds from the Senior Secured Term Loan due 2029 and the private placement to prepay the Senior Secured Term Loan due 2026, inclusive of the outstanding principal amount, accrued interest and prepayment premium. -75- Table of Contents Cash Flow Discussion As of December 31, 2024, we had cash, cash equivalents, and marketable securities of $249.9 million.
Proceeds from the private placement, net of offering costs, were $29.8 million. We used proceeds from the Senior Secured Term Loan due 2029 and the private placement to prepay the Senior Secured Term Loan due 2026, inclusive of the outstanding principal amount, accrued interest and prepayment premium.
As of December 31, 2024, an aggregate of $164.2 million worth of shares remain available to be issued and sold under the ATM program. In October 2023, we entered into the Senior Secured Term Loan due 2029. This transaction resulted in net proceeds of $387.4 million, after deducting fees and expenses.
Under the Merger Agreement, we are prohibited from offering to sell any additional shares of our common stock under the ATM program. -78- Table of Contents In October 2023, we entered into the Senior Secured Term Loan due 2029. This transaction resulted in net proceeds of $387.4 million, after deducting fees and expenses.
Additionally, Pombiliti ® + Opfolda ® has been granted orphan drug designation or status in the U.S., U.K., Switzerland and Japan and data exclusivity in the E.U. -72- Table of Contents Consolidated Results of Operations The following discussion should be read in conjunction with the Consolidated Financial Statements and related notes included elsewhere in this report.
Additionally, Pombiliti ® + Opfolda ® has been granted orphan drug designation or status in the U.S., U.K., Switzerland and Japan and data exclusivity in the E.U.
Net Cash Used in Operating Activities Net cash used in operations for the year ended December 31, 2024 was $33.9 million.
Cash, Cash Equivalents, Marketable Securities, and Restricted Cash," in our Notes to Consolidated Financial Statements. Net Cash Provided by (Used in) Operating Activities Net cash provided by operations for the year ended December 31, 2025 was $33.1 million.
These purchase obligations are in addition to amounts recorded on our December 31, 2024 Consolidated Balance Sheets. We have no off-balance sheet arrangements as of December 31, 2024 and 2023. Recent Accounting Pronouncements Please refer to "— Note 2. Summary of Significant Accounting Policies," in our Notes to the Consolidated Financial Statements.
Recent Accounting Pronouncements Please refer to "— Note 2. Summary of Significant Accounting Policies," in our Notes to the Consolidated Financial Statements.
We have historically funded our operations through stock offerings, product revenues, debt issuance, collaborations, and other financing arrangements. Sources of Liquidity In November 2022, we entered into a Sales Agreement with Goldman Sachs & Co.
We have historically funded our operations through stock offerings, product revenues, debt issuance, collaborations, and other financing arrangements. The Merger Agreement with BioMarin includes restrictions on the conduct of our business prior to the completion of the Merger or termination of the Merger Agreement.
Net cash provided by financing activities was partially offset by the $408.0 million repayment of our Senior Secured Loan due in 2026, and $17.9 million for payments of employee withholding taxes related to restricted stock unit vesting. -76- Table of Contents Funding Requirements We expect to continue to incur significant costs in the foreseeable future primarily due to research and development expenses, including expenses related to conducting clinical trials.
Funding Requirements We expect to continue to incur significant costs in the foreseeable future primarily due to research and development expenses, including expenses related to conducting clinical trials.
As a result of this early extinguishment, a loss on extinguishment of debt of $13.9 million was recognized in the Consolidated Statements of Operations. Other (Expense) Income . The $6.4 million variance was primarily related to the movement in foreign exchange rates caused by remeasurement of foreign-denominated balances. Income Tax Expense.
Restructuring charges in the prior year were primarily related to an initiative to reduce operating costs by abandoning a lease that we no longer believed was useful in our operations. Other (Expense) Income . The $19.7 million variance was primarily related to the movement in foreign exchange rates caused by remeasurement of foreign-denominated balances. Income Tax Expense.
The net cash used in operations was also impacted by an increase in accounts payable and accrued expenses of $49.2 million, associated with accrued interest due to timing, inventory purchases to support our continued commercial growth, personnel costs, and an increase in sales rebates associated with increased commercial sales.
The changes in operating assets and liabilities were primarily driven by an increase in inventory of $111.5 million to support our continued commercial growth , partially offset by an $82.8 million increase in accounts payable and accrued expenses . Net cash used in operations for the year ended December 31, 2024 was $33.9 million.
Selling, General, and Administrative Expense. Selling, general, and administrative expense increased $48.1 million, primarily driven by personnel costs resulting from an increase in the number of employees to support our commercial launch activities, external costs required to support the manufacture and sale of our commercial products, and third-party professional fees. Restructuring Charges.
Selling, General, and Administrative Expense. Selling, general, and administrative expense increased $60.1 million, primarily driven by higher personnel costs and additional legal and professional fees in connection with our intellectual property litigation and the signing of the Merger Agreement with BioMarin. Restructuring Charges.
Cost of goods sold includes manufacturing costs for our commercial products as well as royalties associated with net product sales of Galafold ® . Cost of goods sold as a percentage of net product sales increased 0.7% primarily due to inventory write-offs associated with validation efforts during the first quarter of 2024. -73- Table of Contents Research and Development Expense.
Cost of goods sold includes manufacturing costs as well as royalties associated with net product sales. Cost of goods sold increased by $20.0 million primarily related to the increase in net product sales.
Item 7. MANAGEMENT'S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS Overview We are a global, patient-dedicated biotechnology company focused on discovering, developing, and delivering novel medicines for rare diseases. We seek to deliver the highest quality therapies that have the potential to obsolete current treatments, provide significant benefits to patients, and be first- or best-in-class.
Item 7. MANAGEMENT'S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS Overview We are a leading, global biotechnology company with a clear and compelling mission to develop and deliver transformative medicines for people living with rare diseases. With extraordinary patient focus, we strive to redefine expectations in rare disease.
As of December 31, 2024, remaining milestones under this agreement were $8.5 million. Refer to "— Note 14. Collaborative Agreements," to the Consolidated Financial Statements for more information. We have a number of binding minimum purchase and manufacturing commitments due to our third-party manufacturers.
We have a number of binding minimum purchase and manufacturing commitments due to our third-party manufacturers. As of December 31, 2025, these purchase and manufacturing obligations totaled $218.8 million, of which $195.7 million and $23.1 million are expected in 2026 and 2027, respectively.
The components of net cash used in operations included the net loss for the year ended December 31, 2023 of $151.6 million and the net change in operating assets and liabilities of $48.0 million offset by $86.1 million of stock compensation and $44.4 million of other non-cash adjustments.
The components of net cash provided by operations primarily reflect net loss of $27.1 million adjusted for non-cash expenses of $99.9 million , which includes $87.4 million of stock compensation and $7.5 million of depreciation expense. This is further driven by a net increase in operating assets and liabilities of $39.6 million .
Removed
The following section generally discusses 2024 and 2023 items and year-to-year comparisons between 2024 and 2023.
Added
On April 30, 2025, we entered into an exclusive license agreement with Dimerix Bioscience Pty Limited ("Dimerix") for the United States commercialization rights of Dimerix' Phase 3 drug candidate, DMX-200 for treatment of Focal Segmental Glomerulosclerosis ("FSGS") and other indications. In exchange for these rights, we paid Dimerix an upfront payment of $30 million.
Removed
Restructuring charges were primarily related to an initiative to reduce operating costs by abandoning a lease that we no longer believe is useful in our operations. Loss on extinguishment of debt. In October 2023, the Company voluntarily prepaid the outstanding principal amount, accrued interest and prepayment premiums of the Senior Secured Term Loan due 2026.
Added
We will be obligated to pay Dimerix for certain success-based development and regulatory milestones for FSGS of up to a maximum aggregate amount of $75 million, regulatory milestones for other indications of up to a maximum aggregate amount of $40 million, commercial milestones of up to a maximum aggregate amount of $445 million, and tiered royalties of DMX-200 net sales in the U.S. ranging from the low-teens to low-twenties.
Removed
During the year ended December 31, 2024, we issued and sold an aggregate of 1,732,204 shares through our ATM program at a weighted-average public offering price of $11.69 per share, resulting in net proceeds of $19.6 million.
Added
Dimerix will continue to fund and execute the ACTION3 study, and we will be responsible for submission and maintenance of the regulatory dossier in the United States, as well as all costs of commercialization activities. Additionally, we will have the exclusive rights to develop DMX-200 in other future indications in the United States.
Removed
Proceeds from the private placement, net of offering costs, were $29.8 million.
Added
Amicus and Dimerix have formed a Joint Steering Committee to align the development and commercialization of DMX-200 in FSGS in U.S. On December 19, 2025, we entered into a Merger Agreement with BioMarin and its wholly owned acquisition subsidiary.
Removed
Net cash used in operations for the year ended December 31, 2023 was $69.1 million.
Added
Under the terms of the Merger Agreement, and in accordance with the DGCL, if the Merger is completed, BioMarin's wholly owned acquisition subsidiary will merge with and into Amicus, and Amicus will continue as the surviving corporation as a wholly owned subsidiary of BioMarin.
Removed
The change in operating assets was primarily due to increases in inventory of $44.6 million, an increase in accounts receivable of $20.1 million associated with increased commercial sales, and an increase in prepaid and other current assets of $8.1 million primarily associated with tax prepayments.
Added
In addition, all shares of our common stock outstanding immediately prior to closing (other than Excluded Shares or Dissenting Shares (as defined in the Merger Agreement)) will be cancelled and converted into the right to receive $14.50 per share in cash, without interest and subject to any applicable withholding of taxes.
Removed
Net cash provided by financing activities for the year ended December 31, 2023 was $61.7 million.
Added
Following completion of the Merger, shares of our common stock will no longer be publicly listed. Refer to "— Note 15.
Removed
Net cash provided by financing activities primarily reflects $387.4 million of net proceeds from the Senior Secured Loan due in 2029, $63.1 million of net proceeds from the issuance of shares in connection with our ATM program, $29.8 million of net proceeds from our private placement with Blackstone, and $10.3 million in proceeds from the exercise of stock options.
Added
Merger Agreement," in our Notes to Consolidated Financial Statements for additional information. -75- Table of Contents Consolidated Results of Operations The following discussion should be read in conjunction with the Consolidated Financial Statements and related notes included elsewhere in this report. The following section generally discusses 2025 and 2024 items and year-to-year comparisons between 2025 and 2024.
Removed
In connection with our collaboration agreement with GlaxoSmithKline ("GSK"), pursuant to which we obtained global rights to develop and commercialize Galafold ® as a monotherapy and in combination with ERT for Fabry disease, GSK is eligible to receive post-approval and sales-based milestones up to $40 million, as well as tiered royalties in the mid-teens in eight major markets outside the U.S.
Added
A portion of Pombiliti ® inventory was expensed as research and development costs prior to regulatory approval and as such, the cost of goods sold and related gross margins are not necessarily indicative of future costs of goods sold and gross margin. -76- Table of Contents Research and Development Expense.
Added
These limitations include, among other things, restrictions on our ability to incur additional indebtedness, issue additional shares of our common stock outside of existing equity plans and enter into or amend certain contracts. Sources of Liquidity In November 2022, we entered into a Sales Agreement with Goldman Sachs & Co.
Added
As of December 31, 2025, an aggregate of $164.2 million worth of shares remain available to be issued and sold under the ATM program.
Added
Net cash provided by financing activities primarily reflects $19.2 million in proceeds from the exercise of stock options, partially offset by $18.3 million for payments of employee withholding taxes related to restricted stock unit vesting. -79- Table of Contents Net cash provided by financing activities for the year ended December 31, 2024 was $5.1 million.
Added
If the Merger is not consummated, we may seek additional funding through public or private financings of debt or equity.
Added
On December 19, 2025, the Company entered into the Merger Agreement with BioMarin. Under the terms of the Merger Agreement, the Company may be required to pay BioMarin a termination fee of $175 million if the Merger Agreement is terminated under specific circumstances described in the Merger Agreement.

Item 7A. Quantitative and Qualitative Disclosures About Market Risk

Market Risk — interest-rate, FX, commodity exposure

6 edited+1 added−1 removed4 unchanged
Biggest changeA hypothetical 100 basis point increase or decrease in the average interest rate on our variable rate debts would result in $4.1 million change in the interest expense as of December 31, 2024. -78- Table of Contents We face foreign exchange risk as a result of entering into transactions denominated in currencies other than U.S. dollars, primarily in British pounds ("GBP").
Biggest changeThe annual average variable interest rate for our variable rate debts during the year ended December 31, 2025 was 10.7%. A hypothetical 100 basis point increase or decrease in the average interest rate on our variable rate debts would result in $4.1 million change in the interest expense as of December 31, 2025.
At December 31, 2024, we had a $400 million Senior Secured Term Loan due 2029 that bears interest at a rate equal to the 3-month Term Secured Overnight Financing Rate ("SOFR"), subject to a 2.5% floor, plus a Term SOFR adjustment of 0.26161% and a margin of 6.25% per year.
At December 31, 2025, we had a $400 million Senior Secured Term Loan due 2029 that bears interest at a rate equal to the 3-month Term Secured Overnight Financing Rate ("SOFR"), subject to a 2.5% floor, plus a Term SOFR adjustment of 0.26161% and a margin of 6.25% per year.
The securities in our investment portfolio are not leveraged, are classified as available-for-sale and, due to the short-term nature, are subject to minimal interest rate risk. We believe that a 1% (100 basis points) change in average interest rates would either increase or decrease the market value of our investment portfolio by $0.4 million as of December 31, 2024.
The securities in our investment portfolio are not leveraged, are classified as available-for-sale and, due to the short-term nature, are subject to minimal interest rate risk. We believe that a 1% (100 basis points) change in average interest rates would either increase or decrease the market value of our investment portfolio by $0.7 million as of December 31, 2025.
We currently do not hedge interest rate exposure and consistent with our investment policy, we do not use derivative financial instruments in our investment portfolio. We are exposed to interest rate risk with respect to variable rate debt.
We currently do not hedge interest rate exposure and consistent with our investment policy, we do not use derivative financial instruments in our investment portfolio. -81- Table of Contents We are exposed to interest rate risk with respect to variable rate debt.
Based on our foreign currency denominated exposures as of December 31, 2024, we believe that a near-term 10% fluctuation of the USD to GBP exchange rate could result in a potential change in the fair value of our net GBP denominated assets and liabilities of approximately $57.4 million. -79- Table of Contents
Based on our foreign currency denominated exposures as of December 31, 2025, we believe that a near-term 10% fluctuation of the U.S. dollar to GBP exchange rate could result in a potential change in the fair value of our net GBP denominated assets and liabilities of approximately $48.6 million.
We are not currently engaged in any foreign currency hedging activities. The current exposures arise primarily from cash, accounts receivable, intercompany receivables and payables, and net product sales denominated in foreign currencies.
We face foreign exchange risk as a result of entering into transactions denominated in currencies other than U.S. dollars, primarily in British pounds ("GBP") and euros ("EUR"). We are not currently engaged in any foreign currency hedging activities. The current exposures arise primarily from cash, accounts receivable, intercompany receivables and payables, and net product sales denominated in foreign currencies.
Removed
The annual average variable interest rate for our variable rate debts during the year ended December 31, 2024 was 11.7%.
Added
Furthermore, we believe that a near-term 10% fluctuation of the U.S. dollar to EUR exchange rate could result in a potential change in the fair value of our net EUR denominated assets and liabilities of approximately $28.5 million. -82- Table of Contents

Other FOLD 10-K year-over-year comparisons