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What changed in Amylyx Pharmaceuticals, Inc.'s 10-K — 2024 vs 2025

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Paragraph-level year-over-year comparison of Amylyx Pharmaceuticals, 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.

+560 added−500 removedSource: 10-K (2026-03-03) vs 10-K (2025-03-04)

Top changes in Amylyx Pharmaceuticals, Inc.'s 2025 10-K

560 paragraphs added · 500 removed · 422 edited across 7 sections

Item 1. Business

Business — how the company describes what it does

108 edited+44 added−14 removed251 unchanged
Biggest changeThe patent families around AMX0035 include those that relate to compositions of a bile acid and a phenylbutyrate compound (including TURSO and 4-PBA) and methods of treating neurodegenerative disease, and its associated causes at a cellular level, using those compositions; specific compositions of a phenylbutyrate compound and a bile acid (including TURSO and 4-PBA) and methods of manufacturing those compositions; methods of treating particular symptoms of ALS and/or reducing the associated AEs with combinations of a phenylbutyrate compound and a bile acid (including TURSO and 4-PBA); methods of treating Alzheimer’s disease and other tauopathies (including progressive supranuclear palsy) with 7 combinations of a phenylbutyrate compound and a bile acid (including sodium phenylbutyrate and TURSO); methods of co-administering other therapeutic drugs with combinations of a phenylbutyrate compound and a bile acid (including sodium phenylbutyrate and TURSO); pharmacokinetic characteristics following the administration of TURSO and sodium phenylbutyrate; methods of reducing the level of certain biomarkers in ALS patients with combinations of sodium phenylbutyrate and TURSO; and methods of treating Wolfram Syndrome with combinations of sodium phenylbutyrate and TURSO.
Biggest changeThe patent families around AMX0035 include those that relate to compositions of a bile acid and a phenylbutyrate compound (including TURSO and 4-PBA) and methods of treating neurodegenerative disease, and its associated causes at a cellular level, using those compositions; specific compositions of a phenylbutyrate compound and a bile acid (including TURSO and 4-PBA) and methods of manufacturing those compositions; methods of co-administering other therapeutic drugs with combinations of a phenylbutyrate compound and a bile acid (including sodium phenylbutyrate and TURSO); methods of treating Wolfram Syndrome with combinations of sodium phenylbutyrate and TURSO; methods of administering combinations of TURSO or a pharmaceutically acceptable salt thereof and 4-PBA or a pharmaceutically acceptable salt thereof to a subject with renal impairment; and methods of treating disorders associated with low levels of C-peptide with combinations of sodium phenylbutyrate and TURSO.
Item 1. Business. Overview Amylyx Pharmaceuticals, Inc. (also referred to as Amylyx, we, our or us) is a clinical-stage pharmaceutical company with a mission to develop and advance novel therapies for communities with high unmet medical needs. We have preclinical and clinical development programs underway in neurodegenerative diseases and endocrine conditions.
Item 1. Business. Overview Amylyx Pharmaceuticals, Inc. (also referred to as Amylyx, we, our or us) is a clinical-stage pharmaceutical company with a mission to develop and advance novel therapies for communities with high unmet medical needs. We have preclinical and clinical development programs underway in endocrine conditions and neurodegenerative diseases.
None of our employees are represented by labor unions or covered by collective bargaining agreements. We consider the relationship with our employees to be good. Our human capital is integral to helping us achieve our goal to end the suffering caused by neurodegenerative diseases and endocrine conditions.
None of our employees are represented by labor unions or covered by collective bargaining agreements. We consider the relationship with our employees to be good. Our human capital is integral to helping us achieve our goal to end the suffering caused by endocrine conditions and neurodegenerative diseases.
HITECH also created four new tiers of civil monetary penalties, amended HIPAA to make civil and criminal penalties directly applicable to business associates, and gave state attorneys general new authority to file civil actions for damages or injunctions in federal courts to enforce HIPAA and seek attorneys’ fees and costs associated with pursuing federal civil actions; 16 • the federal Physician Payments Sunshine Act, created under the ACA, and its implementing regulations, which require manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program to report annually to the Centers for Medicare and Medicaid Services, or CMS, under the Open Payments Program, information related to payments or other transfers of value made to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), to certain non-physician providers such as physician assistants and nurse practitioners, and to teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members; • federal price reporting laws, which require manufacturers 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 approved products; • federal consumer protection and unfair competition laws, which broadly regulate marketplace activities and activities that potentially harm consumers; and • analogous state and foreign laws and regulations, such as state and foreign anti-kickback, false claims, consumer protection and unfair competition laws which may apply to pharmaceutical business practices, including but not limited to, research, distribution, sales and marketing arrangements as well as submitting claims involving healthcare items or services reimbursed by any third-party payor, including commercial 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 federal government that otherwise restricts payments that may be made to healthcare providers and other potential referral sources; state laws that require drug manufacturers to file reports with states regarding pricing and marketing information, such as the tracking and reporting of gifts, compensations and other remuneration and items of value provided to healthcare professionals and entities; state and local laws requiring the registration of pharmaceutical sales representatives; and state and foreign laws governing the privacy and security of health information in certain circumstances, many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts.
HITECH also created four new tiers of civil monetary penalties, amended HIPAA to make civil and criminal penalties directly applicable to business associates, and gave state attorneys general new authority to file civil actions for damages or injunctions in federal courts to enforce HIPAA and seek attorneys’ fees and costs associated with pursuing federal civil actions; • the federal Physician Payments Sunshine Act, created under the ACA, and its implementing regulations, which require manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program to report annually to the Centers for Medicare and Medicaid Services, or CMS, under the Open Payments Program, information related to payments or other transfers of value made to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), to certain non-physician providers such as physician assistants and nurse practitioners, and to teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members; • federal price reporting laws, which require manufacturers 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 approved products; • federal consumer protection and unfair competition laws, which broadly regulate marketplace activities and activities that potentially harm consumers; and • analogous state and foreign laws and regulations, such as state and foreign anti-kickback, false claims, consumer protection and unfair competition laws which may apply to pharmaceutical business practices, including but not limited to, research, distribution, sales and marketing arrangements as well as submitting claims involving healthcare items or services reimbursed by any third-party payor, including commercial 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 federal government that otherwise restricts payments that may be made to healthcare providers and other potential referral sources; state laws that require drug manufacturers to file reports with states regarding pricing and marketing information, such as the tracking and reporting of gifts, compensations and other remuneration and items of value provided to healthcare professionals and entities; state and local laws requiring the registration of pharmaceutical sales representatives; and state and foreign laws governing the privacy and security of health information in certain circumstances, many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts.
Like the AKS, the Patient Protection and Affordable Care Act, or the ACA, amended the intent standard for certain healthcare fraud statutes under HIPAA such that a person or entity no longer needs to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation; • HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009, or HITECH, and their respective implementing regulations, which impose requirements on certain covered healthcare providers, health plans, and healthcare clearinghouses as well as their respective business associates that perform services for them that involve the creation, use, receipt, maintenance or disclosure of individually identifiable health information, relating to the privacy, security and transmission of individually identifiable health information.
Like the AKS, the Patient Protection and Affordable Care Act, or the ACA, amended the intent standard for certain healthcare fraud statutes under HIPAA such that a person or entity no longer needs to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation; • HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009, or HITECH, and their respective implementing regulations, which impose requirements on certain covered 16 healthcare providers, health plans, and healthcare clearinghouses as well as their respective business associates that perform services for them that involve the creation, use, receipt, maintenance or disclosure of individually identifiable health information, relating to the privacy, security and transmission of individually identifiable health information.
Additionally, a drug may be eligible for designation as a breakthrough therapy if the product is intended, alone or in combination with one or more other drugs or biologics, to treat a serious or life-threatening condition and preliminary clinical 13 evidence indicates that the product may demonstrate substantial improvement over currently approved therapies on one or more clinically significant endpoints.
Additionally, a drug may be eligible for designation as a breakthrough therapy if the product is intended, alone or in combination with one or more other drugs or biologics, to treat a serious or life-threatening condition and preliminary clinical evidence indicates that the product may demonstrate substantial improvement over currently approved therapies on one or more clinically significant endpoints.
The Inflation Reduction Act of 2022, or IRA, includes several provisions that may impact our business to varying degrees, including provisions that reduce the out-of-pocket spending cap for Medicare Part D beneficiaries from $7,050 to $2,000 starting in 2025, thereby effectively eliminating the coverage gap; impose new manufacturer financial liability on certain drugs under Medicare Part D, allow the U.S. government to negotiate Medicare Part B and Part D price caps for certain high-cost drugs and biologics without generic or biosimilar competition; require companies to pay rebates to Medicare for certain drug prices that increase faster than inflation; and delay until January 1, 2032 the implementation of the HHS rebate rule that would have limited the fees that pharmacy benefit managers can charge.
The Inflation Reduction Act of 2022, or IRA, included several provisions that may impact our business to varying degrees, including provisions that reduce the out-of-pocket spending cap for Medicare Part D beneficiaries from $7,050 to $2,000 starting in 2025, thereby effectively eliminating the coverage gap; impose new manufacturer financial liability on certain drugs under Medicare Part D, allow the U.S. government to negotiate Medicare Part B and Part D price caps for certain high-cost drugs and biologics without generic or biosimilar competition; require companies to pay rebates to Medicare for certain drug prices that increase faster than inflation; and delay until January 1, 2032 the implementation of the HHS rebate rule that would have limited the fees that pharmacy benefit managers can charge.
With the growing availability of new 26 treatments, research, and technologies, we are dedicated to leading this movement in neurodegenerative and endocrine diseases. As collaborators rooted in connection, we ask for input from the community early and often. We push through barriers in the treatment journey in an effort to generate breakthroughs that will make a real difference.
With the growing availability of new treatments, research, and technologies, we are dedicated to leading this movement in neurodegenerative and endocrine diseases. As collaborators rooted in connection, we ask for input from the community early and often. We push through barriers in the treatment journey in an effort to generate breakthroughs that will make a real difference.
Written IND safety reports must be submitted to the FDA and investigators for serious and unexpected suspected AEs, findings from other studies or animal or in vitro testing that suggest a significant risk for human 10 subjects and any clinically important increase in the rate of a serious suspected adverse reaction over that listed in the protocol or investigator brochure.
Written IND safety reports must be submitted to the FDA and investigators for serious and unexpected suspected AEs, findings from other studies or animal or in vitro testing that suggest a significant risk for human subjects and any clinically important increase in the rate of a serious suspected adverse reaction over that listed in the protocol or investigator brochure.
The FDCA also provides three years of market exclusivity for an NDA, 505(b)(2) NDA or supplement to an existing NDA if new clinical investigations, other than bioavailability studies, that were conducted or sponsored by the applicant are deemed by the FDA to be essential to the approval of the application, for example, new indications, dosages or strengths of an existing drug.
The FDCA also provides three years of market exclusivity for an NDA, 505(b)(2) NDA or supplement to an existing NDA if new clinical investigations, other than bioavailability studies, that were conducted or sponsored by the applicant are deemed by the FDA to be essential to the approval of the application, for example, new indications, dosages or strengths of 14 an existing drug.
The FDA will initially review an NDA for completeness before it accepts it for “filing.” Under the FDA’s procedures, the agency has 60 days from its receipt of the NDA to determine whether the application will be accepted for filing based on the agency’s threshold determination that the application is sufficiently complete to permit substantive review.
The FDA will initially 11 review an NDA for completeness before it accepts it for “filing.” Under the FDA’s procedures, the agency has 60 days from its receipt of the NDA to determine whether the application will be accepted for filing based on the agency’s threshold determination that the application is sufficiently complete to permit substantive review.
The most common form of the disease is sporadic ALS, with more than 90% of people with ALS showing no clear family history. In preclinical studies, treatment with AMX0114 resulted in potent, dose-dependent, and durable reduction in CAPN2 mRNA and calpain-2 protein levels in disease-relevant cell models of axonal degeneration.
The most common form of the disease is sporadic ALS, with more than 90% of people with ALS showing no clear family history. 5 In preclinical studies, treatment with AMX0114 resulted in potent, dose-dependent, and durable reduction in CAPN2 mRNA and calpain-2 protein levels in disease-relevant cell models of axonal degeneration.
CMS decides whether and to what extent a new drug product will be covered and reimbursed under Medicare, and private payors tend to follow CMS to a substantial degree. However, no uniform policy of coverage and reimbursement for drug products exists among third-party payors and coverage and reimbursement levels for drug products 24 can differ significantly from payor to payor.
CMS decides whether and to what extent a new drug product will be covered and reimbursed under Medicare, and private payors tend to follow CMS to a substantial degree. However, no uniform policy of coverage and reimbursement for drug products exists among third-party payors and coverage and reimbursement levels for drug products can differ significantly from payor to payor.
Coverage and reimbursement by a third-party payor may depend upon a number of factors, including the third-party payor’s determination that use of a drug product is: • a covered benefit under its health plan; • safe, effective and medically necessary; • appropriate for the specific patient; • cost-effective; and • neither experimental nor investigational.
Coverage and reimbursement by a third-party payor may depend upon a number of factors, including the third-party payor’s determination that use of a drug product is: • a covered benefit under its health plan; • safe, effective and medically necessary; 25 • appropriate for the specific patient; • cost-effective; and • neither experimental nor investigational.
This translated to improved neuronal survival and reductions in extracellular neurofilament light chain, or NfL levels, a broadly researched biomarker for 5 axonal degeneration in ALS, across multiple disease models and paradigms of neuronal injury. AMX0114 was generally well tolerated in in vivo preclinical safety studies.
This translated to improved neuronal survival and reductions in extracellular neurofilament light chain, or NfL levels, a broadly researched biomarker for axonal degeneration in ALS, across multiple disease models and paradigms of neuronal injury. AMX0114 was generally well tolerated in in vivo preclinical safety studies.
Supply and Manufacturing We rely, and expect to continue to rely for the foreseeable future, on third-party contract manufacturing organizations, or CMOs, for the production of avexitide, AMX0035 and AMX0114 in compliance with current Good Manufacturing Process, or cGMP, requirements, for use in clinical trials under the guidance of members of our organization.
Supply and Manufacturing We rely, and expect to continue to rely for the foreseeable future, on third-party contract manufacturing organizations, or CMOs, for the production of avexitide, AMX0035, AMX0114, and AMX0318 in compliance with current Good Manufacturing Process, or cGMP, requirements, for use in clinical trials under the guidance of members of our organization.
The patent relates to use of TURSO in the treatment of ALS in a mammal. An opposition has been filed to the grant of EP3016654 at the European Patent Office, or EPO, asking the EPO to 8 revoke EP3016654. The EPO issued a preliminary opinion on November 18, 2019 finding that at least the main claim of EP3016654 lacked novelty.
The patent relates to use of TURSO in the treatment of ALS in a mammal. An opposition has been filed to the grant of EP3016654 at the European Patent Office, or EPO, asking the EPO to revoke EP3016654. The EPO issued a preliminary opinion on November 18, 2019 finding that at least the main claim of EP3016654 lacked novelty.
Accordingly, this review process typically takes 12 months and 8 months, respectively from the date the NDA is submitted to the FDA. The FDA does not always meet its PDUFA goal dates for standard or priority NDAs, and the review process is often extended by FDA requests for additional information or 11 clarification.
Accordingly, this review process typically takes 12 months and 8 months, respectively from the date the NDA is submitted to the FDA. The FDA does not always meet its PDUFA goal dates for standard or priority NDAs, and the review process is often extended by FDA requests for additional information or clarification.
Outside of the U.S., the pricing of pharmaceutical products is subject to governmental control in many countries. For example, in the EU, pricing and reimbursement schemes vary widely from country to country. Some countries provide that 25 products may be marketed only after a reimbursement price has been agreed.
Outside of the U.S., the pricing of pharmaceutical products is subject to governmental control in many countries. For example, in the EU, pricing and reimbursement schemes vary widely from country to country. Some countries provide that products may be marketed only after a reimbursement price has been agreed.
HELIOS (NCT05676034) is a single-site, single-arm, open-label, proof of biology, Phase 2 trial designed to study the effect of AMX0035 on safety and tolerability, and various measures of endocrinological, neurological, and ophthalmologic function in adult participants living with Wolfram syndrome.
HELIOS is a single-site, single-arm, open-label, proof of biology, Phase 2 trial designed to study the effect of AMX0035 on safety and tolerability, and various measures of endocrinological, neurological, and ophthalmologic function in adult participants living with Wolfram syndrome.
We seek to preserve the integrity and confidentiality of our data and trade secrets by maintaining physical security of our premises and physical and electronic security of our information technology, or IT, systems. While we have confidence in our agreements and security measures, either may be breached, and we may not have adequate remedies.
We seek to preserve the integrity and confidentiality of our data and trade secrets by maintaining physical security of our premises and physical and electronic security of our information technology, or IT, systems. While we have confidence in our agreements 8 and security measures, either may be breached, and we may not have adequate remedies.
Fast Track Designation applies to both the product and the specific indication for which it is being studied. The sponsor can request the FDA to designate the product for Fast Track status any time before receiving NDA approval, but ideally no later than the pre-NDA meeting.
Fast Track Designation applies to both the product and the specific indication for which it is being studied. The 13 sponsor can request the FDA to designate the product for Fast Track status any time before receiving NDA approval, but ideally no later than the pre-NDA meeting.
Available Information We file Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K, proxy statements and other information with the SEC. Our filings with the SEC are available on the SEC’s website at www.sec.gov. We also maintain a website at http://www.amylyx.com.
Available Information We file Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K, proxy statements and other information with the SEC. Our filings with the SEC are available on the SEC’s website at www.sec.gov. We also maintain a website at www.amylyx.com.
In 15 addition to new legislation, FDA regulations, guidance, and policies are often revised or reinterpreted by the agency in ways that may significantly affect the manner in which pharmaceutical products are regulated and marketed. Other U.S.
In addition to new legislation, FDA regulations, guidance, and policies are often revised or reinterpreted by the agency in ways that may significantly affect the manner in which pharmaceutical products are regulated and marketed. Other U.S.
Our approach to drug development accounts for the fast disease progression following long diagnosis timelines, significant heterogeneity in patient populations, the need to deepen the understanding of pathophysiology, and lack of consensus on measures of clinical benefit in drug development.
Our approach to drug development accounts for the fast disease progression following long diagnosis timelines, significant heterogeneity in patient populations, the need to deepen the understanding of pathophysiology, and lack of consensus on measures of clinical 27 benefit in drug development.
If and when those conditions have been met to the FDA’s satisfaction, the FDA will typically issue an 12 approval letter. An approval letter authorizes commercial marketing of the drug with specific prescribing information for specific indications.
If and when those conditions have been met to the FDA’s satisfaction, the FDA will typically issue an approval letter. An approval letter authorizes commercial marketing of the drug with specific prescribing information for specific indications.
These requirements include compliance with EU cGMP standards when manufacturing medicinal products and active pharmaceutical ingredients, including the manufacture of active pharmaceutical ingredients outside of the EU with the intention to import the active pharmaceutical ingredients into the EU. • The marketing and promotion of authorized medicinal products, including industry-sponsored continuing medical education and advertising directed toward the prescribers of medicinal products and/or the general public, are strictly regulated in the EU notably under Directive 2001/83/EC83EC, as amended, and are also subject to EU Member State national laws.
These requirements include compliance with EU cGMP standards when manufacturing medicinal products and active pharmaceutical ingredients, including the manufacture of active pharmaceutical ingredients outside of the EU with the intention to import the active pharmaceutical ingredients into the EU. • The marketing and promotion of authorized medicinal products, including industry-sponsored continuing medical education and advertising directed toward the prescribers of medicinal products and/or the general public, are strictly regulated in the EU notably under Directive 2001/83/EC, as amended, and are also subject to EU Member State national laws.
It also requires the submission to the relevant competent authorities of a marketing authorization application, or MAA, and granting of a marketing authorization by these authorities before the product can be marketed and sold in the EU. 18 Clinical Trial Approval In April 2014, the EU adopted the new Clinical Trials Regulation (EU) No 536/2014, or Clinical Trials Regulation, which replaced the Clinical Trials Directive 2001/20/EC on January 31, 2022.
It also requires the submission to the relevant competent authorities of a marketing authorization application, or MAA, and granting of a marketing authorization by these authorities before the product can be marketed and sold in the EU. 19 Clinical Trial Approval In April 2014, the EU adopted the new Clinical Trials Regulation (EU) No 536/2014, or Clinical Trials Regulation, which replaced the Clinical Trials Directive 2001/20/EC on January 31, 2022.
Pediatric exclusivity, if granted, adds six months to existing regulatory exclusivity periods for all formulations, dosage forms, and indications of the active 14 moiety and patent terms.
Pediatric exclusivity, if granted, adds six months to existing regulatory exclusivity periods for all formulations, dosage forms, and indications of the active moiety and patent terms.
Environmental Most of our employees choose to work remotely, but we maintain features such as recycling programs and automatic lighting at our facilities to minimize our impact.
Environmental Most of our employees choose to work remotely, but we maintain features such as recycling programs, composting and automatic lighting at our facilities to minimize our impact.
Any authorization which is not followed by the actual placing of the medicinal product on the EU market (in case of centralized procedure) or on the market of the authorizing EU Member State (for a nationally 21 authorized product) within three years after authorization, or if the product is removed from the market for three consecutive years, ceases to be valid (the so-called sunset clause).
Any authorization which is not followed by the actual placing of the medicinal product on the EU market (in case of centralized procedure) or on the market of the authorizing EU Member State (for a nationally 22 authorized product) within three years after authorization, or if the product is removed from the market for three consecutive years, ceases to be valid (the so-called sunset clause).
As part of our governance practices, we are committed to high standards of ethics, which are reflected in our Code of Business Conduct and Ethics, which applies to our directors, officers, employees and designated agents. This Code is posted on our corporate 27 website. We have an independent chairman, and five of our seven board members are independent.
As part of our governance practices, we are committed to high standards of ethics, which are reflected in our Code of Business Conduct and 28 Ethics, which applies to our directors, officers, employees and designated agents. This Code is posted on our corporate website. We have an independent chairman, and five of our seven board members are independent.
The co-owned with, and in-licensed patent family from, Stanford University relates to liquid pharmaceutical formulations of exendin(9-39). There are 2 issued U.S. patents and 5 issued foreign patents in this family. We also have patent applications pending in this family in the U.S., EU, and other jurisdictions.
The co-owned with, and in-licensed patent family from, Stanford University relates to liquid pharmaceutical formulations of exendin(9-39). There are 2 issued U.S. patents and 44 issued foreign patents in this family. We also have patent applications pending in this family in the U.S., EU, and other jurisdictions.
Our lead investigational asset is avexitide, an investigational, first-in-class glucagon-like peptide-1, or GLP-1 receptor antagonist. Avexitide has been evaluated as a treatment for PBH and congenital HI, two indications characterized by hyperinsulinemic hypoglycemia. The U.S.
Our lead investigational asset is avexitide, a first-in-class glucagon-like peptide-1, or GLP-1, receptor antagonist. Avexitide has been evaluated as a treatment for PBH and congenital hyperinsulinism, or Congenital HI, two indications characterized by hyperinsulinemic hypoglycemia. The U.S.
If a concerned EU Member State cannot approve the assessment report and related materials due to 20 concerns relating to a potential serious risk to public health, disputed elements may be referred to the European Commission, whose decision is binding on all EU Member States.
If a concerned EU Member State cannot approve the assessment report and related materials due to 21 concerns relating to a potential serious risk to public health, disputed elements may be referred to the European Commission, whose decision is binding on all EU Member States.
The Board of Appeal overturned in oral proceedings held on June 5, 2024, the decision of the Opposition Division and maintained EP3016654 in limited form. The patent as maintained in limited form protects TUDCA for use in the treatment of ALS only. As such, EP3016654 as maintained has no relevance for PSP or Wolfram Syndrome.
The Board of Appeal overturned in oral proceedings held on June 5, 2024, the decision of the Opposition Division and maintained EP3016654 in limited form. The patent as maintained in limited form protects TUDCA for use in the treatment of ALS only. As such, EP3016654 as maintained has no relevance for Wolfram Syndrome.
In particular, in 2010, the Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act of 2010, or collectively, the ACA, was enacted, which, among other things, subjected biologic products to potential competition by lower-cost biosimilars; increased the minimum Medicaid rebates owed by most manufacturers under the Medicaid Drug Rebate Program; extended the Medicaid Drug Rebate program to utilization of prescriptions of individuals enrolled in Medicaid managed care organizations; subjected manufacturers to new annual fees and taxes for certain branded prescription drugs; created the Medicare Part D coverage gap discount program, in which manufacturers must agree to 70% point-of-sale discounts off negotiated prices of applicable brand drugs to eligible beneficiaries during their coverage gap period, as a condition for the manufacturer’s outpatient drugs to be covered under Medicare Part D; and provided incentives to programs that increase the federal government’s comparative effectiveness research.
In particular, in 2010, the Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act of 2010, or collectively, the ACA, was enacted, which, among other things, subjected biologic products to potential competition by lower-cost biosimilars; increased the minimum Medicaid rebates owed by most manufacturers under the Medicaid Drug Rebate Program; extended the Medicaid Drug Rebate program to utilization of prescriptions of individuals enrolled in Medicaid managed care organizations; subjected manufacturers to new annual fees and taxes for certain branded prescription drugs; created the Medicare Part D coverage gap discount program (later replaced by the Manufacturer Discount Program under the Inflation Reduction Act of 2022), in which manufacturers must agree to 70% point-of-sale discounts off negotiated prices of applicable brand drugs to eligible beneficiaries during their coverage gap period, as a condition for the manufacturer’s outpatient drugs to be covered under Medicare Part D; and provided incentives to programs that increase the federal government’s comparative effectiveness research.
The process required by the FDA before a drug may be marketed in the U.S. generally involves the following: • Completion of preclinical laboratory tests, animal studies and formulation studies in compliance with the FDA’s good laboratory practice, or GLP, regulations; • Submission to the FDA of an IND, which must become effective before human clinical trials may begin; • Approval by an independent institutional review board, or IRB, at each clinical site before each trial may be initiated; • Performance of adequate and well-controlled human clinical trials in accordance with Good Clinical Practices, or GCP, requirements to establish the safety and efficacy of the proposed drug product for each indication; • Submission to the FDA of an NDA, including payment of application user fees; • A determination by the FDA within 60 days of its receipt of a new drug application, or an NDA to accept the marketing application for review; • Satisfactory completion of an FDA advisory committee review, if applicable; • Satisfactory completion of an FDA inspection of the manufacturing facility or facilities at which the product is produced to assess compliance with cGMP, requirements and to assure that the facilities, methods and controls are adequate to preserve the product’s identity, strength, quality and purity; • Satisfactory completion of FDA audits of clinical trial sites to assure compliance with GCPs and the integrity of the clinical data; and • FDA review and approval of the NDA. 9 Preclinical Studies Preclinical studies include laboratory evaluation of product chemistry, toxicity and formulation, as well as in vitro and animal studies to assess potential safety and efficacy.
The process required by the FDA before a drug may be marketed in the U.S. generally involves the following: • Completion of preclinical laboratory tests, animal studies and formulation studies in compliance with the FDA’s good laboratory practice, or GLP, regulations; • Submission to the FDA of an IND, which must become effective before human clinical trials may begin; • Approval by an independent institutional review board, or IRB, at each clinical site before each trial may be initiated; • Performance of adequate and well-controlled human clinical trials in accordance with Good Clinical Practices, or GCP, requirements to establish the safety and efficacy of the proposed drug product for each indication; • Submission to the FDA of an NDA, including payment of application user fees; • A determination by the FDA within 60 days of its receipt of a new drug application, or an NDA to accept the marketing application for review; 9 • Satisfactory completion of an FDA advisory committee review, if applicable; • Satisfactory completion of an FDA inspection of the manufacturing facility or facilities at which the product is produced to assess compliance with cGMP, requirements and to assure that the facilities, methods and controls are adequate to preserve the product’s identity, strength, quality and purity; • Satisfactory completion of FDA audits of clinical trial sites to assure compliance with GCPs and the integrity of the clinical data; and • FDA review and approval of the NDA.
Any patents to issue from this family may first begin to expire as early as October 15, 2039, not accounting for any patent term adjustment or extensions or terminal disclaimers, and assuming that all applicable annuity and/or maintenance fees are paid timely. Another family relates to the treatment of congenital HI with exendin(9-39).
The issued patent and others that issue from this family may first begin to expire as early as October 15, 2039, not accounting for any patent term adjustment or extensions or terminal disclaimers, and assuming that all applicable annuity and/or maintenance fees are paid timely. Another family relates to the treatment of Congenital HI with exendin(9-39).
Products that are granted a marketing authorization with the results of the pediatric clinical trials conducted in accordance with the PIP (even where such results are negative) are eligible for six months’ supplementary protection certificate, or SPC, extension (provided an application for such extension is made at the same time as filing the SPC application for the product, or at any point up to 2 years before the SPC expires). 19 The centralized procedure provides for the grant of a single marketing authorization by the European Commission that is valid across the EEA.
Products that are granted a marketing authorization with the results of the pediatric clinical trials conducted in accordance with the PIP (even where such results are negative) are eligible for six months’ supplementary protection certificate, or SPC, extension (provided an application for such extension is made at the same time as filing the SPC application for the product, or at any point up to 2 years before the SPC expires). 20 The centralized procedure provides for the grant of a single marketing authorization by the European Commission that is valid throughout the EEA.
The ESG Committee, formed in 2023, helps the Executive Leadership Team to develop strategy relating to ESG matters and support the integration of strategically significant ESG policies into the Company’s business operations and strategy. Given our reliance on outsourced operations, it is important that we select partners whose standards align with our own.
Our ESG Committee helps the Executive Leadership Team to develop strategy relating to ESG matters and support the integration of strategically significant ESG policies into the Company’s business operations and strategy. Given our reliance on outsourced operations, it is important that we select partners whose standards align with our own.
Although no patents have yet issued from this family, we expect the term on patents issuing from this family to extend until at least April 2044, not accounting for any patent term adjustment or extensions or terminal disclaimers, and assuming that all applicable annuity and/or maintenance fees are paid timely. AMX0035 Our patent portfolio around AMX0035 includes ten patent families.
Although no patents have yet issued from this family, we expect the term on patents issuing from this family to extend until at least April 22, 2044, not accounting for any patent term adjustment or extensions or terminal disclaimers, and assuming that all applicable annuity and/or maintenance fees are paid timely. 7 AMX0035 Our patent portfolio around AMX0035 includes fifteen patent families.
Human clinical trials are typically conducted in three sequential phases, which may overlap or be combined: • Phase 1: The drug is initially introduced into healthy human subjects or patients with the target disease or condition and tested for safety, dosage tolerance, absorption, metabolism, distribution, excretion and, if possible, to gain an early indication of its effectiveness. • Phase 2: The drug is administered to a limited patient population to identify possible adverse effects and safety risks, to preliminarily evaluate the efficacy of the product for specific targeted diseases and to determine dosage tolerance and optimal dosage. • Phase 3: The drug is administered to an expanded patient population, generally at geographically dispersed clinical trial sites, in well-controlled clinical trials to generate enough data to statistically evaluate the efficacy and safety of the product for approval, to establish the overall risk-benefit profile of the product, and to provide adequate information for the labeling of the product.
Human clinical trials are typically conducted in three sequential phases, which may overlap or be combined: • Phase 1: The drug is initially introduced into healthy human subjects or patients with the target disease or condition and tested for safety, dosage tolerance, absorption, metabolism, distribution, excretion and, if possible, to gain an early indication of its effectiveness. • Phase 2: The drug is administered to a limited patient population to identify possible adverse effects and safety risks, to preliminarily evaluate the efficacy of the product for specific targeted diseases and to determine dosage tolerance and optimal dosage. • Phase 3: The drug is administered to an expanded patient population, generally at geographically dispersed clinical trial sites, in well-controlled clinical trials to generate enough data to statistically evaluate the efficacy and safety of the product for approval, to establish the overall risk-benefit profile of the product, and to provide adequate information for the labeling of the product. 10 Post-approval trials, sometimes referred to as Phase 4 clinical trials, may be conducted after initial marketing approval.
The two in-licensed patent families from Stanford University relate to treatment of hyperinsulinemic hypoglycemia with GLP-1 antagonist exendin(9-39). There are 7 issued U.S. patents and 81 issued foreign patents in these two families. We also have patent applications pending in these two families in the U.S., EU, and other jurisdictions.
The two in-licensed patent families from Stanford University relate to treatment of hyperinsulinemic hypoglycemia with GLP-1 antagonist exendin(9-39). There are 8 issued U.S. patents and 83 issued foreign patents in these two families. We also have patent applications pending in these two families in the U.S., EU, and other jurisdictions.
Food and Drug Administration, or the FDA, has granted avexitide Breakthrough Therapy Designation for both post-bariatric hypoglycemia, or PBH and congenital hyperinsulinism, or HI, Rare Pediatric Disease Designation in congenital HI, and Orphan Drug Designation for the treatment of hyperinsulinemic hypoglycemia.
Food and Drug Administration, or the FDA, has granted avexitide Breakthrough Therapy Designation for both PBH and HI, Rare Pediatric Disease Designation in Congenital HI, and Orphan Drug Designation for the treatment of hyperinsulinemic hypoglycemia.
Healthcare Reform Legislation Payors, whether domestic or foreign, or governmental or private, are developing increasingly sophisticated methods of controlling healthcare costs and those methods are not always specifically adapted for new technologies such as gene therapy and therapies addressing rare diseases such as those we are developing.
Current and Future U.S. Healthcare Reform Legislation Payors, whether domestic or foreign, or governmental or private, are developing increasingly sophisticated methods of controlling healthcare costs and those methods are not always specifically adapted for new technologies such as gene therapy and therapies addressing rare diseases such as those we are developing.
Other countries may allow companies to fix their own prices for products, but monitor and control product volumes and issue guidance to physicians to limit prescriptions. Efforts to control prices and utilization of pharmaceutical products will likely continue as countries attempt to manage healthcare expenditures. Employees and Human Capital As of December 31, 2024, we had 123 full-time employees.
Other countries may allow companies to fix their own prices for products, but monitor and control product volumes and issue guidance to physicians to limit prescriptions. Efforts to control prices and utilization of pharmaceutical products will likely continue as countries attempt to manage healthcare expenditures. 26 Employees and Human Capital As of December 31, 2025, we had 136 full-time employees.
Also included are the two patent families relating to avexitide that are solely owned by us. One family relates to the treatment of hyperinsulinemic hypoglycemia with exendin(9-39). There are currently no issued patents in this family. We have patent applications pending in this family in the U.S., EU, and other jurisdictions.
Also included are the two patent families relating to avexitide that are solely owned by us. One family relates to the treatment of hyperinsulinemic hypoglycemia with exendin(9-39). There is one issued foreign patent in this family. We have patent applications pending in this family in the U.S., EU, and other jurisdictions.
The primary efficacy objective of LUCIDITY is to evaluate the FDA-agreed primary endpoint of reduction in the composite of Level 2 and Level 3 hypoglycemic events through Week 16. Safety and tolerability will also be evaluated.
The primary efficacy objective of LUCIDITY is to evaluate the FDA-agreed primary outcome of reduction in the composite of Level 2 and Level 3 hypoglycemic events through Week 16. Safety and tolerability will also be evaluated. Recruitment of LUCIDITY is complete.
Our Audit, Nominating and Corporate Governance, and Compensation Committees are comprised solely of independent directors. 28
Our Audit, Nominating and Corporate Governance, and Compensation Committees are comprised solely of independent directors. 29
In 2024, we adopted a formal ESG charter to support our ongoing commitment to environmental, health and safety, corporate social responsibility, corporate governance, sustainability, and other related trends, issues, and concerns relevant to the Company.
We have a formal ESG charter to support our ongoing commitment to environmental, health and safety, corporate social responsibility, corporate governance, sustainability, and other related trends, issues, and concerns relevant to the Company.
We also offer dental and vision insurance. We complement these offerings with options for a Flexible Spending Account, or FSA, or Health Savings Account, or HSA for eligible medical expenses, Dependent Care FSA for child or elder care expenses, and a Limited Purpose FSA for dental and vision expenses.
We complement these offerings with options for a Flexible Spending Account, or FSA, or Health Savings Account for eligible medical expenses, Dependent Care FSA for child or elder care expenses, and a Limited Purpose FSA for dental and vision expenses.
Bruschettini has no procedural option to broaden the claims at this point. A European divisional application is not pending in this family and cannot be filed anymore.
Bruschettini has no procedural option to broaden the claims at this point. A European divisional application is not pending in this family and can no longer be filed.
Such authorization is intended for products for which the applicant can demonstrate that it is unable to provide comprehensive data on the efficacy and safety under normal conditions of use, because either (i) the indications for which the product in question is intended are encountered so rarely that the applicant cannot reasonably be expected to provide comprehensive evidence; (ii) in the present state of scientific knowledge, comprehensive information cannot be provided; or (iii) it would be contrary to generally accepted principles of medical ethics to collect such information.
The European Commission may grant a so-called “marketing authorization under exceptional circumstances.” Such authorization is intended for products for which the applicant can demonstrate that it is unable to provide comprehensive data on the efficacy and safety under normal conditions of use, because either (i) the indications for which the product in question is intended are encountered so rarely that the applicant cannot reasonably be expected to provide comprehensive evidence; (ii) in the present state of scientific knowledge, comprehensive information cannot be provided; or (iii) it would be contrary to generally accepted principles of medical ethics to collect such information.
The legislation aims at simplifying and streamlining the approval of clinical trials in the EU; for example, the Clinical Trials Regulation provides for a streamlined application procedure via a single-entry point, rules on the protection of subjects and informed consent, transparency requirements, and strictly defined deadlines for the assessment of clinical trial applications.
The legislation aims at simplifying and streamlining the approval of clinical trials in the EU; for example, the Clinical Trials Regulation provides for a streamlined application procedure via the Clinical Trials Information System ("CTIS"), which serves as the single-entry point for submission and assessment of clinical trial application in the EU, rules on the protection of subjects and informed consent, transparency requirements, and strictly defined deadlines for the assessment of clinical trial applications.
Other potential consequences include, among other things: • Restrictions on the marketing or manufacturing of the product, complete withdrawal of the product from the market or product recalls; • Fines, warning letters or holds on post-approval clinical trials; • Refusal of the FDA to approve pending NDAs or supplements to approved NDAs, or suspension or withdrawal of product approvals; • Product seizure or detention, or refusal to permit the import or export of products; and • Injunctions or the imposition of civil or criminal penalties.
Other potential consequences include, among other things: • Restrictions on the marketing or manufacturing of the product, complete withdrawal of the product from the market or product recalls; • Fines, warning letters or holds on post-approval clinical trials; • Refusal of the FDA to approve pending NDAs or supplements to approved NDAs, or suspension or withdrawal of product approvals; • Product seizure or detention, or refusal to permit the import or export of products; and • Injunctions or the imposition of civil or criminal penalties. 15 The FDA strictly regulates marketing, labeling, advertising and promotion of products that are placed on the market.
AMX0035 also prevented cell death in neuronal cells derived from people with Wolfram syndrome and significantly delayed progression of the diabetes phenotype in a WFS1-knock-out preclinical model. In October 2024, we announced positive topline data from the Phase 2 open-label HELIOS clinical trial of AMX0035 in 12 adults living with Wolfram syndrome.
AMX0035 also prevented cell death in neuronal cells derived from people with Wolfram syndrome and significantly delayed progression of the diabetes phenotype in a WFS1-knock-out preclinical model. In May 2025, we announced positive Week 48 data from the Phase 2 open-label HELIOS (NCT05676034) clinical trial of AMX0035 in 12 adults living with Wolfram syndrome.
Although no patents have issued from the latest patent family around AMX0035, we expect the term of patents issued from that family to extend until at least September 2043, not accounting for any patent term adjustment or extensions or terminal disclaimers, and assuming that all applicable annuity and/or maintenance fees are paid timely.
Although no patents have issued from the latest-expiring patent families around AMX0035, we expect the term of patents issued from those families to extend until at least March 2045, not accounting for any patent term adjustment or extensions or terminal disclaimers, and assuming that all applicable annuity and/or maintenance fees are paid timely.
Numerous other U.S. states have passed similarly comprehensive consumer privacy laws which may vary in their scope and application, and enforcement will likely remain unpredictable for the foreseeable future. Other states have passed privacy legislation which applies specifically to consumer health data.
Numerous other U.S. states have passed similarly comprehensive consumer privacy laws which may vary in their scope and application, and enforcement will likely remain unpredictable for the foreseeable future.
Where the CHMP gives a positive opinion, the EMA provides the opinion together with supporting documentation to the European Commission, who makes the final decision to grant a marketing authorization, which is issued within 67 days of receipt of the EMA’s recommendation. The European Commission may grant a so-called “marketing authorization under exceptional circumstances”.
Where the CHMP gives a positive opinion, the EMA provides the opinion together with supporting documentation to the European Commission, who makes the final decision to grant a marketing authorization, which is issued within 67 days of receipt of the EMA’s recommendation.
In addition to the competitive benefits above, we offer: • Hybrid Work Environment: We are primarily remote but have opportunities to come together as a full organization • Touchpoints Rooted in Connection: Our in-person Anchor Weeks and bi-weekly Amylyx Exchange calls help us collaborate and connect with each other and the communities we’re serving • Learning and Development Program: Opportunities to grow professionally and network • Recognition Platform: Recognizes employees beyond just the day-to-day • “Take It As You Need It” Paid Time Off: Paid time off designed with flexibility for vacation, personal needs, school events, or appointments • Employee Assistance Program: Access to mental health support, work-life solutions, financial resources, and legal guidance • Paid Parental Leave: Ability to take time off and connect with your new child • Mobile Reimbursement: Monthly cell phone reimbursement to stay connected We affirm our commitment to a diverse and inclusive workplace by ensuring equitable compensation for all employees and upholding the principles of pay equity across all levels of the organization.
In addition to the competitive benefits above, we offer: • Hybrid-Remote Work Environment: We are primarily remote but have opportunities to come together as a full organization • Robust Onboarding Program: Led by a cross-functional team, this program introduces new employees to the organization • Touchpoints Rooted in Connection: Our in-person Anchor Weeks and bi-weekly Amylyx Exchange calls help us collaborate and connect with each other and the communities we’re serving • Internal Social Channels: These channels allow us to share and amplify business updates and foster informal connections • Learning and Development Program: Opportunities to grow professionally and network • Recognition Platform: Recognizes employees beyond just the day-to-day • Flexible Paid Time Off: Paid time off designed with flexibility for vacation, personal needs, school events, or appointments • Employee Assistance Program: Access to mental health support, work-life solutions, financial resources, and legal guidance • Paid Parental Leave: Ability to take time off and connect with your new child • Mobile Reimbursement: Monthly cell phone reimbursement to stay connected We affirm our commitment to a diverse and inclusive workplace by ensuring equitable compensation for all employees and upholding the principles of pay equity across all levels of the organization.
No participants withdrew due to AEs. • In the Phase 2b, 28-day, open-label, investigator-initiated, crossover trial (N=16), 90 mg once daily and 45 mg twice daily of avexitide met its primary endpoint and significantly reduced rates of hypoglycemic events in participants following RYGB surgery and other upper-gastrointestinal surgeries.
No participants withdrew due to AEs. • In the Phase 2b, 28-day, open-label, investigator-initiated, crossover trial (n=16), 90 mg once daily and 45 mg twice daily of avexitide met its primary endpoint and significantly reduced rates of hypoglycemic events in participants following a variety of upper gastrointestinal surgeries, including RYGB, sleeve gastrectomy, esophagectomy, Nissen fundoplication, and gastrectomy.
Post-approval trials, sometimes referred to as Phase 4 clinical trials, may be conducted after initial marketing approval. These trials are used to gain additional experience from the treatment of patients in the intended therapeutic indication. In certain instances, the FDA may mandate the performance of Phase 4 clinical trials as a condition of approval on an NDA.
These trials are used to gain additional experience from the treatment of patients in the intended therapeutic indication. In certain instances, the FDA may mandate the performance of Phase 4 clinical trials as a condition of approval on an NDA.
As an employer, diversity is also important, including having representation of diverse views and backgrounds at the highest levels of the organization. Three of our eight senior executives are women, and two of our seven board members are women. We care deeply about supporting and investing in our people.
As an employer, diversity is also important, including having representation of diverse views and backgrounds at the highest levels of the organization. Three of our eight senior executives are women, and two of our seven board members are women.
In those ten families, we currently own a total of 164 issued patents and pending patent applications. Currently, our patent portfolio around AMX0035 includes seven issued U.S. patents and 67 issued foreign patents. We also have pending applications in the U.S., EU and other jurisdictions.
In those fifteen families, we currently own a total of 156 issued patents and pending patent applications. Currently, our patent portfolio around AMX0035 includes 9 issued U.S. patents and 71 issued foreign patents. We also have pending applications in the U.S., EU and other jurisdictions.
We have long-term, single-source supply agreements in place for our active pharmaceutical ingredients, and single-source arrangements for the manufacturing and packaging of bulk drug at established CMOs for clinical trials and other potential needs. We have built a team of pharmaceutical industry technical operations leaders.
We have development and/or supply agreements in place for our active pharmaceutical ingredients, and for the manufacturing and packaging of drug product at established CMOs for clinical trials and other potential development needs. We have built a team of pharmaceutical industry technical operations leaders.
Recently, many countries in the EU have increased the amount of discounts required on pharmaceuticals and these efforts could continue as countries attempt to manage health care expenditures, especially in light of the severe fiscal and debt crises experienced by many countries in the EU.
Recently, many countries in the EU have increased the amount of discounts required on pharmaceuticals and these efforts could continue as countries attempt to manage health care expenditures, especially in light of the severe fiscal and debt crises experienced by many countries in the EU. The downward pressure on health care costs in general, particularly prescription products, has become intense.
HELIOS showed improvement in pancreatic beta cell function, as measured by C-peptide response after 24 weeks of treatment with AMX0035, the study’s primary efficacy endpoint, in contrast to the expected decrease in pancreatic function with disease progression.
In October 2024, we announced positive topline data from HELIOS at week 24. HELIOS showed improvement in pancreatic beta cell function, as measured by C-peptide response after 24 weeks of treatment with AMX0035, the study’s primary efficacy endpoint, in contrast to the expected decrease in pancreatic function with disease progression.
Some countries may require the completion of additional cost effectiveness assessments that compare the cost-effectiveness of a particular product candidate to currently available therapies or so-called health technology assessments, in order to obtain reimbursement or pricing approval.
Some countries provide that products may be marketed only after a reimbursement price has been agreed. Some countries may require the completion of additional cost effectiveness assessments that compare the cost-effectiveness of a particular product candidate to currently available therapies or so-called health technology assessments, in order to obtain reimbursement or pricing approval.
The remaining patent family, which is co-owned by us and Stanford University, relates to methods of improving nutrition in subjects, including individuals who have undergone gastrointestinal surgery, by avexitide therapy. We have a Patent Cooperation Treaty, or PCT application pending in this family.
The remaining patent family, which is co-owned by us and Stanford University, relates to methods of improving nutrition in subjects, including individuals who have undergone gastrointestinal surgery, by avexitide therapy. We have patent applications pending in this family in the U.S., EU, and other jurisdictions.
After evaluating the NDA and all related information, including the advisory committee recommendation, if any, and inspection reports regarding the manufacturing facilities and clinical trial sites, the FDA may issue an approval letter, or, in some cases, a Complete Response Letter.
Additionally, before approving an NDA, the FDA may inspect one or more clinical trial sites to assure compliance with GCP requirements. 12 After evaluating the NDA and all related information, including the advisory committee recommendation, if any, and inspection reports regarding the manufacturing facilities and clinical trial sites, the FDA may issue an approval letter, or, in some cases, a Complete Response Letter.
The conduct of preclinical studies is subject to federal regulations and requirements, including good laboratory practice regulations for safety/toxicology studies. An IND sponsor must submit the results of the preclinical tests, together with manufacturing information, analytical data and any available clinical data or literature and plans for clinical studies, among other things, to the FDA as part of an IND.
An IND sponsor must submit the results of the preclinical tests, together with manufacturing information, analytical data and any available clinical data or literature and plans for clinical studies, among other things, to the FDA as part of an IND.
Due to the Statutory Pay-As-You-Go Act of 2010, estimated budget deficit increases resulting from the American Rescue Plan Act of 2021, and subsequent legislation, Medicare payments to providers were further reduced starting on January 1, 2025; however, legislation has been introduced in the U.S. Congress that would reverse these payment reductions.
Due to the Statutory Pay-As-You-Go Act of 2010, estimated budget deficit increases resulting from the American Rescue Plan Act of 2021, and subsequent legislation, Medicare payments to providers were further reduced starting on January 1, 2025.
As of December 31, 2024, our patent estate included 20 issued U.S. patents, 25 pending U.S. patent applications, 211 granted foreign patents, and 109 pending foreign patent applications. 6 Avexitide We acquired a patent portfolio directed to avexitide from Eiger Pharmaceuticals, Inc., or Eiger, in June 2024.
As of December 31, 2025, our patent estate included 23 issued U.S. patents, 257 granted foreign patents, over 15 pending U.S. patent applications, and over 115 pending foreign patent applications. Avexitide We acquired a patent portfolio directed to avexitide from Eiger Pharmaceuticals, Inc., or Eiger, in July of 2024.
The FDA will not approve an application unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and adequate to assure consistent production of the product within required specifications. Additionally, before approving an NDA, the FDA may inspect one or more clinical trial sites to assure compliance with GCP requirements.
The FDA will not approve an application unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and adequate to assure consistent production of the product within required specifications.
In addition, the Drug Supply Chain Security Act, or DSCSA, was enacted in 2013 with the aim of building an electronic system to identify and trace certain prescription drugs and biologics distributed in the United States. Changes to the manufacturing process are strictly regulated and often require prior FDA approval before being implemented.
In addition, the Drug Supply Chain Security Act, or DSCSA, was enacted in 2013 with the aim of building an electronic system to identify and trace certain prescription drugs and biologics distributed in the United States.
The FDA strictly regulates marketing, labeling, advertising and promotion of products that are placed on the market. Drugs may be promoted by a manufacturer and any third parties acting on behalf of a manufacturer only for the approved indications and in a manner consistent with the approved label for the product.
Drugs may be promoted by a manufacturer and any third parties acting on behalf of a manufacturer only for the approved indications and in a manner consistent with the approved label for the product.
Any product candidates that we successfully develop and commercialize may compete with current therapies and new therapies that may become available in the future. We believe that the key competitive factors affecting the success of any of our product candidates will include efficacy, safety profile, dosing, cost, effectiveness of promotional support and intellectual property protection.
We believe that the key competitive factors affecting the success of any of our product candidates will include efficacy, safety profile, dosing, cost, effectiveness of promotional support and intellectual property protection.
Compliance with the GDPR will be a rigorous and time-intensive process that may increase the cost of doing business or require companies to change their business practices to ensure full compliance. Brexit and the Regulatory Framework in the United Kingdom The UK formally left the EU on January 31, 2020.
Compliance with the GDPR will be a rigorous and time-intensive process that may increase the cost of doing business or require companies to change their business practices to ensure full compliance.
The safety profile of AMX0035 in HELIOS was consistent with prior safety data from the study of AMX0035 in ALS. All AEs were mild or moderate, and there were no serious AEs related to AMX0035 treatment. We plan to share Week 48 data from the ongoing HELIOS trial of AMX0035 in Wolfram syndrome in 2025.
The safety profile of AMX0035 in HELIOS data at Week 48 and Week 24 were consistent with prior safety data from the studies of AMX0035. All AEs were mild or moderate, and there were no serious AEs related to AMX0035 treatment. We continue to work with the FDA on a Phase 3 trial in Wolfram syndrome.

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

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Biggest changeRisks Related to Our Business Operations and Employee Matters • We are currently operating in a period of economic uncertainty and capital markets disruption, which has been significantly impacted by geopolitical instability, ongoing military conflicts, including the ongoing war between Russia and Ukraine, the Israel-Hamas conflict and conflict in the Middle East, a new U.S. presidential administration and accompanying regulatory activities and economic policies, events related thereto, and changes in inflation and interest rates, any of which could have a material adverse effect on our business, financial condition and results of operations. • We depend heavily on our executive officers, principal consultants and others, and the loss of their services would materially harm our business. • We only have a limited number of employees to manage and operate our business. • We are continuously evaluating and pursuing strategic transactions, and may pursue strategic transactions in the future that are aligned with our mission to improve our underlying business performance.
Biggest changeRisks Related to Our Business Operations and Employee Matters • We are continuously evaluating and pursuing strategic transactions, and cannot guarantee that previous or future strategic transactions, acquisitions or business combinations pursued to further our mission to improve our underlying business performance will, in fact, produce any benefits. • We depend heavily on our executive officers, principal consultants and others, and the loss of their services would materially harm our business. • We only have a limited number of employees to manage and operate our business. • We are currently operating in a period of economic uncertainty, which has been significantly impacted by geopolitical instability, ongoing military conflicts, including the ongoing war between Russia and Ukraine, the ongoing conflicts in the Middle East, the evolving regulatory activities and policy changes under the current U.S. government, events related thereto, and changes in inflation and interest rates, any of which could have a material adverse effect on our business, financial condition and results of operations.
We will not return to profitability unless and until we successfully commercialize any of our current or future product candidates. Our ability to once again become and remain profitable depends on our ability to generate revenue.
We will not return to profitability unless and until we successfully commercialize any of our current or future product candidates. Our ability to once again become and to remain profitable depends on our ability to generate revenue.
It is possible that one or more of the active moieties in AMX0035 has also been approved by FDA or other regulatory authorities.
It is possible that one or more of the active moieties in AMX0035 has also been approved by the FDA or other regulatory authorities.
For example, if we are unable to identify programs that ultimately result in approved products, we may spend material amounts of our capital and other resources evaluating, acquiring and developing products that ultimately do not provide a return on our investment. Competitive products may reduce or eliminate the commercial opportunity for AMX0035 for our intended indications or avexitide.
For example, if we are unable to identify programs that ultimately result in approved products, we may spend material amounts of our capital and other resources evaluating, acquiring and developing products that ultimately do not provide a return on our investment. Competitive products may reduce or eliminate the commercial opportunity for avexitide or AMX0035 for our intended indications.
Risks Related to Our Dependence on Third Parties We rely on third parties to assist in conducting our clinical trials.
Risks Related to Our Dependence on Third Parties We rely on third parties to assist in conducting our clinical trials.
As a result, we currently rely on third parties for the manufacture and supply of the active pharmaceutical ingredients, or APIs, in AMX0035 and avexitide, and for the blending and packaging of AMX0035 and avexitide in accordance with applicable law, regulations and standards.
As a result, we currently rely on third parties for the manufacture and supply of the active pharmaceutical ingredients, or APIs, in avexitide and AMX0035, and for the blending and packaging of avexitide and AMX0035 in accordance with applicable law, regulations and standards.
Although we believe that there are several potential alternative manufacturers who could manufacture each of the APIs in AMX0035 and avexitide, we may incur added costs and delays in identifying and qualifying any such replacement.
Although we believe that there are several potential alternative manufacturers who could manufacture each of the APIs in avexitide and AMX0035, we may incur added costs and delays in identifying and qualifying any such replacement.
We may be unable to conclude agreements for commercial supply with third-party manufacturers, or may be unable to do so on acceptable terms. There may be difficulties in scaling up to commercial quantities and formulation of AMX0035 and avexitide, and the costs of manufacturing could be prohibitive.
We may be unable to conclude agreements for commercial supply with third-party manufacturers, or may be unable to do so on acceptable terms. There may be difficulties in scaling up to commercial quantities and formulation of avexitide and AMX0035, and the costs of manufacturing could be prohibitive.
The risks described elsewhere pertaining to our intellectual property rights also apply to the intellectual property rights that we may in-license, and any failure by us or our licensors to obtain, maintain, defend and enforce these rights could have an adverse effect on our business.
The risks described elsewhere pertaining to our intellectual property rights also apply to the intellectual property rights that we license or may in-license, and any failure by us or our licensors to obtain, maintain, defend and enforce these rights could have an adverse effect on our business.
Delaware law and provisions in our amended and restated certificate of incorporation, or our certificate of incorporation, and amended and restated bylaws, or our bylaws, could make a merger, tender offer or proxy contest difficult, thereby depressing the trading price of our common stock.
Delaware law and provisions in our certificate of incorporation and amended and restated bylaws, or our bylaws, could make a merger, tender offer or proxy contest difficult, thereby depressing the trading price of our common stock.
Acquisitions and business combinations may involve a number of risks, the occurrence of which could adversely affect our business, reputation, operating results and financial condition, including: • diversion of management’s attention; • disruption to our existing operations and plans; • inability to effectively manage our expanded operations; • difficulties or delays in integrating and assimilating information and financial systems, operations, manufacturing processes and products of an acquired business or other business venture or in realizing projected efficiencies, growth prospects, cost savings, and synergies; • inability to successfully integrate or develop a distribution channel for acquired product lines; • potential loss of key employees, customers, distributors, or sales representatives of the acquired businesses or adverse effects on existing business relationships with suppliers, customers, distributors, and sales representatives; 77 • adverse impact on overall profitability if our expanded operations do not achieve the financial results projected in our valuation models; • assumption of contracts, liabilities and other agreements associated with acquired assets, including royalty or other payments due under such agreements; • reallocation of amounts of capital from other operating initiatives and/or an increase in our leverage and debt service requirements to pay acquisition purchase prices or other business venture investment costs, which could in turn restrict our ability to access additional capital when needed or pursue other important elements of our business strategy; • infringement by acquired businesses or other business ventures of intellectual property rights of others; • violation of confidentiality, intellectual property and non-compete obligations or agreements by employees of an acquired business or lack of or inadequate formal intellectual property protection mechanisms in place at an acquired business; • inaccurate assessment of additional post-acquisition investments, undisclosed, contingent or other liabilities or problems, unanticipated costs associated with an acquisition, and an inability to recover or manage such liabilities and costs; • incorrect estimates made in the accounting for acquisitions and incurrence of non-recurring charges; and • write-off of significant amounts of goodwill or other assets as a result of deterioration in the performance of an acquired business or product line, adverse market conditions, changes in the competitive landscape, changes in laws or regulations that restrict activities of an acquired business or product line, or as a result of a variety of other circumstances.
Acquisitions and business combinations may involve a number of risks, the occurrence of which could adversely affect our business, reputation, operating results and financial condition, including: • diversion of management’s attention; • disruption to our existing operations and plans; • inability to effectively manage our expanded operations; • difficulties or delays in integrating and assimilating information and financial systems, operations, manufacturing processes and products of an acquired business or other business venture or in realizing projected efficiencies, growth prospects, cost savings, and synergies; 79 • inability to successfully integrate or develop a distribution channel for acquired product lines; • potential loss of key employees, customers, distributors, or sales representatives of the acquired businesses or adverse effects on existing business relationships with suppliers, customers, distributors, and sales representatives; • adverse impact on overall profitability if our expanded operations do not achieve the financial results projected in our valuation models; • assumption of contracts, liabilities and other agreements associated with acquired assets, including royalty or other payments due under such agreements; • reallocation of amounts of capital from other operating initiatives and/or an increase in our leverage and debt service requirements to pay acquisition purchase prices or other business venture investment costs, which could in turn restrict our ability to access additional capital when needed or pursue other important elements of our business strategy; • infringement by acquired businesses or other business ventures of intellectual property rights of others; • violation of confidentiality, intellectual property and non-compete obligations or agreements by employees of an acquired business or lack of or inadequate formal intellectual property protection mechanisms in place at an acquired business; • inaccurate assessment of additional post-acquisition investments, undisclosed, contingent or other liabilities or problems, unanticipated costs associated with an acquisition, and an inability to recover or manage such liabilities and costs; • incorrect estimates made in the accounting for acquisitions and incurrence of non-recurring charges; and • write-off of significant amounts of goodwill or other assets as a result of deterioration in the performance of an acquired business or product line, adverse market conditions, changes in the competitive landscape, changes in laws or regulations that restrict activities of an acquired business or product line, or as a result of a variety of other circumstances.
Among other things, our certificate of incorporation and bylaws: • permit our board of directors to issue up to 10,000,000 shares of preferred stock, with any rights, preferences and privileges as they may designate (including the right to approve an acquisition or other change in our control); • provide that the authorized number of directors may be changed only by resolution of the board of directors; • provide that our board of directors or any individual director may only be removed with cause and the affirmative vote of the holders of at least 66-2/3% of the voting power of all of our then-outstanding common stock; • provide that all vacancies, including newly created directorships, may, except as otherwise required by law, be filled by the affirmative vote of a majority of directors then in office, even if less than a quorum; • divide our board of directors into three classes; • require that any action to be taken by our stockholders must be effected at a duly called annual or special meeting of stockholders and not be taken by written consent; • provide that stockholders seeking to present proposals before a meeting of stockholders or to nominate candidates for election as directors at a meeting of stockholders must provide notice in writing in a timely manner and also specify requirements as to the form and content of a stockholder’s notice; • do not provide for cumulative voting rights (therefore allowing the holders of a majority of the shares of common stock entitled to vote in any election of directors to elect all of the directors standing for election, if they should so choose); • provide that special meetings of our stockholders may be called only by the board of directors pursuant to a resolution adopted by a majority of the total number of authorized directors; and • provide that the Court of Chancery of the State of Delaware is the sole and exclusive forum for the following types of actions or proceedings under state, statutory and common law: (i) any derivative action or proceeding brought on our behalf; (ii) any action or proceeding asserting a claim of breach of a fiduciary duty owed by any of our current or former directors, officers or other employees to us or our stockholders; (iii) any action or proceeding asserting a claim against us or any of our current or former directors, officers or other employees, arising out of or pursuant to any provision of the Delaware General Corporation Law, our certificate of incorporation or our bylaws; (iv) any action or proceeding to interpret, apply, enforce or determine the validity of our certificate of incorporation or our bylaws; (v) any action or proceeding as to which the Delaware General Corporation Law confers jurisdiction to the Court of Chancery of the State of Delaware; and (vi) any action asserting a claim against us or any of our directors, officers or other employees governed by the internal affairs doctrine, in all cases to the fullest extent permitted by law and subject to the court’s having personal jurisdiction 84 over the indispensable parties named as defendants; provided these provisions of our certificate of incorporation and bylaws will not apply to suits brought to enforce a duty or liability created by the Exchange Act, or any other claim for which the federal courts have exclusive jurisdiction; and provided that, unless we consent in writing to the selection of an alternative forum, to the fullest extent permitted by law, the federal district courts of the U.S. shall be the exclusive forum for the resolution of any complaint asserting a cause of action arising under the Securities Act of 1933, as amended, or the Securities Act.
Among other things, our certificate of incorporation and bylaws: • permit our board of directors to issue up to 10,000,000 shares of preferred stock, with any rights, preferences and privileges as they may designate (including the right to approve an acquisition or other change in our control); • provide that the authorized number of directors may be changed only by resolution of the board of directors; • provide that our board of directors or any individual director may only be removed with cause and the affirmative vote of the holders of at least 66-2/3% of the voting power of all of our then-outstanding common stock; • provide that all vacancies, including newly created directorships, may, except as otherwise required by law, be filled by the affirmative vote of a majority of directors then in office, even if less than a quorum; • divide our board of directors into three classes; • require that any action to be taken by our stockholders must be effected at a duly called annual or special meeting of stockholders and not be taken by written consent; • provide that stockholders seeking to present proposals before a meeting of stockholders or to nominate candidates for election as directors at a meeting of stockholders must provide notice in writing in a timely manner and also specify requirements as to the form and content of a stockholder’s notice; • do not provide for cumulative voting rights (therefore allowing the holders of a majority of the shares of common stock entitled to vote in any election of directors to elect all of the directors standing for election, if they should so choose); • provide that special meetings of our stockholders may be called only by the board of directors pursuant to a resolution adopted by a majority of the total number of authorized directors; and • provide that the Court of Chancery of the State of Delaware is the sole and exclusive forum for the following types of actions or proceedings under state, statutory and common law: (i) any derivative action or proceeding brought on our behalf; (ii) any action or proceeding asserting a claim of breach of a fiduciary duty owed by any of our current or former directors, officers or other employees to us or our stockholders; (iii) any action or proceeding asserting a claim against us or any of our current or former directors, officers or other employees, arising out of or pursuant to any provision of the Delaware General Corporation Law, our certificate of incorporation or our bylaws; (iv) any action or proceeding to interpret, apply, enforce or determine the validity of our certificate of incorporation or our bylaws; (v) any action or proceeding as to which the Delaware General Corporation Law confers jurisdiction to the Court of Chancery of the State of Delaware; and (vi) any action asserting a claim against us or any of our directors, officers or other employees governed by the internal affairs doctrine, in all cases to the fullest extent permitted by law and subject to the court’s having personal jurisdiction over the indispensable parties named as defendants; provided these provisions of our certificate of incorporation and bylaws will not apply to suits brought to enforce a duty or liability created by the Exchange Act, or any other claim for which the federal courts have exclusive jurisdiction; and provided that, unless we consent in writing to the selection of an alternative forum, to the fullest extent permitted by law, the federal district courts of the U.S. shall be the exclusive forum for the resolution of any complaint asserting a cause of action arising under the Securities Act.
The FDA may determine that an NDA for avexitide, if approved, does not meet the eligibility criteria for a priority review voucher, including for the following reasons: • Congenital HI no longer meets the definition of a rare pediatric disease; • the NDA contains an active ingredient that has been previously approved by the FDA; • the NDA does not rely on clinical data derived from studies examining a pediatric population and dosages of the drug intended for that population (that is, if the NDA does not contain sufficient clinical data to allow for adequate labeling for use by the full range of affected pediatric patients); or 50 • the NDA is approved for a different adult indication than the rare pediatric disease for which avexitide is designated.
The FDA may determine that an NDA for avexitide, if approved, does not meet the eligibility criteria for a priority review voucher, including for the following reasons: • Congenital HI no longer meets the definition of a rare pediatric disease; • the NDA contains an active ingredient that has been previously approved by the FDA; • the NDA does not rely on clinical data derived from studies examining a pediatric population and dosages of the drug intended for that population (that is, if the NDA does not contain sufficient clinical data to allow for adequate labeling for use by the full range of affected pediatric patients); or • the NDA is approved for a different adult indication than the rare pediatric disease for which avexitide is designated.
Factors relating to our business that may contribute to these fluctuations include the following, as well as other factors described elsewhere in this Annual Report: • our ability to manufacture and deliver supply of avexitide or AMX0035; • our ability to maintain market acceptance of our product and product candidates, if approved, as a treatment option; • delays or failures in advancement of existing or future development candidates into the clinic or product candidates in clinical trials; • the feasibility of developing, manufacturing, and commercializing our product and product candidates; • our ability to manage our growth; • the outcomes of research programs, clinical trials or other product development or approval processes; • our ability to successfully develop avexitide and AMX0035 for additional indications and to commercialize avexitide and AMX0035 for such additional indications, if approved; • risks associated with the international aspects of our business including the conduct of clinical trials in multiple locations and potential commercialization in such locations; • our ability to accurately report our financial results in a timely manner; • our dependence on, and the need to attract and retain, key management and other personnel; • our ability to obtain, protect and enforce our IP rights; • our ability to prevent the theft or misappropriation of our IP, know-how or technologies; • advantages that our competitors and potential competitors may have in securing funding, obtaining the rights to critical IP or developing competing technologies or products; • our ability to obtain additional capital that may be necessary to expand our business; • business interruptions such as power outages, strikes, acts of terrorism or natural disasters; and • the ultimate impact of global economic and geopolitical events.
Factors relating to our business that may contribute to these fluctuations include the following, as well as other factors described elsewhere in this Annual Report: • our ability to manufacture and deliver clinical supply of avexitide or AMX0035; • our ability to obtain regulatory approval for our product candidates; • our ability to maintain market acceptance of our product and product candidates, if approved, as a treatment option; • delays or failures in advancement of existing or future development candidates into the clinic or product candidates in clinical trials; • the feasibility of developing, manufacturing, and commercializing our product and product candidates; • our ability to manage our growth; • the outcomes of research programs, clinical trials or other product development or approval processes; • our ability to successfully develop avexitide and AMX0035 for additional indications and to commercialize avexitide and AMX0035 for such additional indications, if approved; • risks associated with the international aspects of our business including the conduct of clinical trials in multiple locations and potential commercialization in such locations; • our ability to accurately report our financial results in a timely manner; • our dependence on, and the need to attract and retain, key management and other personnel; • our ability to obtain, protect and enforce our IP rights; • our ability to prevent the theft or misappropriation of our IP, know-how or technologies; • advantages that our competitors and potential competitors may have in securing funding, obtaining the rights to critical IP or developing competing technologies or products; • our ability to obtain additional capital that may be necessary to expand our business; • business interruptions such as power outages, strikes, acts of terrorism or natural disasters; and • the ultimate impact of domestic and global economic and geopolitical events.
We may also experience numerous unforeseen events during our clinical trials that could delay or prevent our ability to receive marketing approval or commercialize avexitide, AMX0035 or any other current or future product candidates we develop, including: • regulators, or institutional review boards, or IRBs, or other reviewing bodies may not authorize us or our investigators to commence a clinical trial, or to conduct or continue a clinical trial at a prospective or specific trial site; • we may not reach agreement on acceptable terms with prospective contract research organizations, or CROs, and clinical trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and trial sites; • the number of subjects or patients required for clinical trials of avexitide, AMX0035 in an indication or any future product candidate may be larger than we anticipate, enrollment in these clinical trials may be insufficient or slower than we anticipate, and the number of clinical trials being conducted at any given time may be high and result in fewer available patients for any given clinical trial, or patients may drop out of these clinical trials at a higher rate than we anticipate; • our third-party contractors, including those manufacturing avexitide, AMX0035 or any other current or future product candidates or conducting clinical trials on our behalf, may fail to comply with regulatory requirements or meet their contractual obligations to us in a timely manner, or at all; • we may have to amend clinical trial protocol submitted to regulatory authorities or conduct additional studies to reflect changes in regulatory requirements or guidance, which we may be required to resubmit to an IRB and regulatory authorities for re-examination; • unforeseen safety events may occur during the course of a clinical trial and these events may result in the temporary suspension or termination of a clinical trial, or require urgent safety measures or restrictions to protect human subjects during the conduct of a clinical trial; • regulators, IRBs or other reviewing bodies may fail to approve or subsequently find fault with the manufacturing processes or facilities of third-party manufacturers with which we enter into agreement for clinical and commercial supplies, or the supply or quality of avexitide, AMX0035 or any other current or future product candidate or other materials necessary to conduct clinical trials of avexitide, AMX0035 or any other current or 40 future product candidates may be insufficient, inadequate or not available at an acceptable cost, or we may experience interruptions in supply; and • the potential for approval policies or regulations of the FDA or any other applicable foreign regulatory agencies to significantly change in a manner rendering our clinical data insufficient for approval.
We may also experience numerous unforeseen events during our clinical trials that could delay or prevent our ability to receive marketing approval or commercialize avexitide, AMX0035, AMX0114, AMX0318 or any other current or future product candidates we develop, including: • regulators, or institutional review boards, or IRBs, or other reviewing bodies may not authorize us or our investigators to commence a clinical trial, or to conduct or continue a clinical trial at a prospective or specific trial site; • we may not reach agreement on acceptable terms with prospective contract research organizations, or CROs, and clinical trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and trial sites; • the number of subjects or patients required for clinical trials of avexitide, AMX0035, AMX0114 and AMX0318 in an indication or any future product candidate may be larger than we anticipate, enrollment in these clinical trials may be insufficient or slower than we anticipate, and the number of clinical trials being conducted at any given time may be high and result in fewer available patients for any given clinical trial, or patients may drop out of these clinical trials at a higher rate than we anticipate; • our third-party contractors, including those manufacturing avexitide, AMX0035, AMX0114, AMX0318 or any other current or future product candidates or conducting clinical trials on our behalf, may fail to comply with regulatory requirements or meet their contractual obligations to us in a timely manner, or at all; • we may have to amend clinical trial protocol submitted to regulatory authorities or conduct additional studies to reflect changes in regulatory requirements or guidance, which we may be required to resubmit to an IRB and regulatory authorities for re-examination; • unforeseen safety events may occur during the course of a clinical trial and these events may result in the temporary suspension or termination of a clinical trial, or require urgent safety measures or restrictions to protect human subjects during the conduct of a clinical trial; • regulators, IRBs or other reviewing bodies may fail to approve or subsequently find fault with the manufacturing processes or facilities of third-party manufacturers with which we enter into agreement for clinical and commercial supplies, or the supply or quality of avexitide, AMX0035, AMX0114, AMX0318 or any other current or future product candidate or other materials necessary to conduct clinical trials of avexitide, AMX0035, AMX0114, AMX0318 or any other current or future product candidates may be insufficient, inadequate or not available at an acceptable cost, or we may experience interruptions in supply; and • the potential for approval policies or regulations of the FDA or any other applicable foreign regulatory agencies to significantly change in a manner rendering our clinical data insufficient for approval.
Our future capital requirements depend on many factors, including: • the scope, progress, results and costs of researching and developing avexitide, AMX0035 for Wolfram syndrome, PSP and potential additional indications, AMX0114, as well as any other product candidates we are currently developing or may in the future develop; • the timing of, and the costs involved in, our efforts to obtain marketing approvals for avexitide in PBH, AMX0035 for the treatment of Wolfram syndrome, PSP and potential additional indications, AMX0114, and our efforts to obtain approvals for other product candidates we are developing or may in the future develop and pursue; • the number of other product candidates that we may pursue and their development requirements; • the costs of commercialization activities for avexitide, AMX0035 and for any approved indications, or any other product candidate that receives regulatory approval to the extent such costs are not the responsibility of any future collaborators, including the costs and timing of establishing sufficient product sales, marketing, distribution and manufacturing capabilities; • subject to receipt of regulatory approval on a jurisdiction-by-jurisdiction basis, revenue, if any, received from commercial sales of avexitide and AMX0035 for any approved indications or any other current or future product candidates; • the extent to which we in-license, acquire, or acquire rights to other products, product candidates or technologies; • our obligation, if any, to pay royalties in connection with the development and commercialization of avexitide or any other products or product candidates we may in-license or acquire; • our headcount fluctuation; • the costs of preparing, filing and prosecuting patent applications, maintaining and protecting our intellectual property rights, including enforcing and defending intellectual property related claims; and • the ongoing costs of operating as a public company.
Our future capital requirements depend on many factors, including: • the scope, progress, results and costs of researching and developing avexitide, AMX0035 for Wolfram syndrome and potential additional indications, AMX0114, AMX0318, as well as any other product candidates we are currently developing or may in the future develop; • the timing of, and the costs involved in, our efforts to obtain marketing approvals for avexitide in PBH, AMX0035 for the treatment of Wolfram syndrome and potential additional indications, AMX0114, AMX0318, and our efforts to obtain approvals for other product candidates we are developing or may in the future develop and pursue; • the number of other product candidates that we may pursue and their development requirements; • the costs of commercialization activities for avexitide, AMX0035 and for any approved indications, or any other product candidate that receives regulatory approval to the extent such costs are not the responsibility of any future collaborators, including the costs and timing of establishing sufficient product sales, marketing, distribution and manufacturing capabilities; • subject to receipt of regulatory approval on a jurisdiction-by-jurisdiction basis, revenue, if any, received from commercial sales of avexitide and AMX0035 for any approved indications or any other current or future product candidates; • the extent to which we in-license, acquire, or acquire rights to other products, product candidates or technologies; • our obligation, if any, to pay royalties in connection with the development and commercialization of avexitide or any other products or product candidates we may in-license or acquire; • our headcount fluctuation; • the costs of preparing, filing and prosecuting patent applications, maintaining and protecting our intellectual property rights, including enforcing and defending intellectual property related claims; and • the ongoing costs of operating as a public company.
Avexitide, AMX0035 and any current or future product candidates could fail to obtain regulatory approvals, and any of our future product candidates could fail to obtain regulatory approvals, for many reasons, including the following: • the FDA or other comparable foreign regulatory authorities may disagree as to the design or implementation of our clinical trials and may require additional data to support regulatory approval; • we may be unable to demonstrate to the satisfaction of the FDA or other comparable foreign regulatory authorities that a product candidate is safe and effective for its proposed indication(s) and, if necessary, that a product candidate and any active components thereof are safe and effective for the proposed indication; • the results of clinical trials may not meet the level of statistical significance required by the FDA or other comparable foreign regulatory authorities for approval; • we may be unable to demonstrate that a product candidate’s clinical and other benefits outweigh its safety risks; • the FDA and comparable authorities in other countries may disagree with our interpretation of data from clinical trials or preclinical studies and our request may require additional trials or studies to support marketing approval; • the data collected from clinical trials of avexitide, AMX0035 or any other current or future product candidates may not be sufficient to support the submission of an NDA or other submission to the FDA or other comparable foreign regulatory authority to obtain regulatory approval in the U.S. or elsewhere; • the FDA or other comparable foreign regulatory authorities may find deficiencies with clinical trial sites or fail to approve the manufacturing processes or facilities of third-party manufacturers with which we contract for clinical and commercial supplies; and • the approval policies or regulations of the FDA or other comparable foreign regulatory authorities may significantly change in a manner rendering our clinical data insufficient for approval.
Avexitide, AMX0035, AMX0114, AMX0318 and any current or future product candidates could fail to obtain regulatory approvals, and any of our future product candidates could fail to obtain regulatory approvals, for many reasons, including the following: • the FDA or other comparable foreign regulatory authorities may disagree as to the design or implementation of our clinical trials and may require additional data to support regulatory approval; • we may be unable to demonstrate to the satisfaction of the FDA or other comparable foreign regulatory authorities that a product candidate is safe and effective for its proposed indication(s) and, if necessary, that a product candidate and any active components thereof are safe and effective for the proposed indication; • the results of clinical trials may not meet the level of statistical significance required by the FDA or other comparable foreign regulatory authorities for approval; • we may be unable to demonstrate that a product candidate’s clinical and other benefits outweigh its safety risks; • the FDA and comparable authorities in other countries may disagree with our interpretation of data from clinical trials or preclinical studies and our request may require additional trials or studies to support marketing approval; • the data collected from clinical trials of avexitide, AMX0035, AMX0114, AMX0318 or any other current or future product candidates may not be sufficient to support the submission of an NDA or other submission to the FDA or other comparable foreign regulatory authority to obtain regulatory approval in the U.S. or elsewhere; • the FDA or other comparable foreign regulatory authorities may find deficiencies with clinical trial sites or fail to approve the manufacturing processes or facilities of third-party manufacturers with which we contract for clinical and commercial supplies; and • the approval policies or regulations of the FDA or other comparable foreign regulatory authorities may significantly change in a manner rendering our clinical data insufficient for approval.
Further, legislation may be introduced that, if passed, would, among other things, further expand the 340B program to additional covered entities or would require participating manufacturers to agree to provide 340B discounted pricing on drugs used in an inpatient setting, and any additional future changes to the definition of average manufacturer price or the Medicaid 64 rebate amount could affect our 340B ceiling price calculations and negatively impact our results of operations.
Further, legislation may be introduced that, if passed, would, among other things, further expand the 340B program to additional covered entities or would require participating manufacturers to agree to provide 340B discounted pricing on drugs used in an inpatient setting, and any additional future changes to the definition of average manufacturer price or the Medicaid rebate amount could affect our 340B ceiling price calculations and negatively impact our results of operations.
If avexitide is approved for future uses and, if AMX0035 is approved for future uses, such as Wolfram syndrome or PSP, or if other current and future candidates, such as AMX0114, are approved with only NCI exclusivity, generic manufacturers may file their ANDAs anytime following approval of avexitide, AMX0035, or AMX0114 and seek to launch their generic products following the expiration of the three year market exclusivity period, even if we still have patent protection for our product.
If avexitide is approved for future uses and, if AMX0035 is approved for future uses, such as Wolfram syndrome, or if other current and future candidates, such as AMX0114, are approved with only NCI exclusivity, generic manufacturers may file their ANDAs anytime following approval of avexitide, AMX0035, or AMX0114 and seek to launch their generic products following the expiration of the three year market exclusivity period, even if we still have patent protection for our product.
Accordingly, in markets outside the U.S., the reimbursement for avexitide, AMX0035 and any other current or future product candidates we may develop may be reduced compared with the U.S. and may be insufficient to generate commercially reasonable revenues and profits. Ongoing healthcare legislative and regulatory reform measures may have a material adverse effect on our business and results of operations.
Accordingly, in markets outside the U.S., the reimbursement for avexitide, AMX0035 and any other current or future product candidates we may develop may be reduced compared with the U.S. and may be insufficient to generate commercially reasonable revenues and profits. 63 Ongoing healthcare legislative and regulatory reform measures may have a material adverse effect on our business and results of operations.
If we or our third-party contractors fail to comply with applicable GCPs, the clinical data generated in our clinical trials may be deemed unreliable and the FDA or other regulatory body may require us to perform additional clinical trials before approving avexitide or AMX0035, including for additional indications, or any 53 other current or future product candidates, which would delay the regulatory approval process.
If we or our third-party contractors fail to comply with applicable GCPs, the clinical data generated in our clinical trials may be deemed unreliable and the FDA or other regulatory body may require us to perform additional clinical trials before approving avexitide or AMX0035, including for additional indications, or any other current or future product candidates, which would delay the regulatory approval process.
In addition, we cannot assure you that any such products that are approved will be manufactured or produced economically, successfully commercialized or widely accepted in the marketplace or be more effective than other commercially available alternatives. 45 Research activities to identify product candidates require substantial technical, financial and human resources, whether or not any product candidates are ultimately identified.
In addition, we cannot assure you that any such products that are approved will be manufactured or produced economically, successfully commercialized or widely accepted in the marketplace or be more effective than other commercially available alternatives. Research activities to identify product candidates require substantial technical, financial and human resources, whether or not any product candidates are ultimately identified.
If we are unable to maintain sufficient insurance coverage at an acceptable cost or to otherwise protect against potential product liability claims, it could prevent or inhibit the development and commercial production and 51 sale of avexitide, AMX0035 or any other current or future product candidates, which could harm our business, financial condition, results of operations and prospects.
If we are unable to maintain sufficient insurance coverage at an acceptable cost or to otherwise protect against potential product liability claims, it could prevent or inhibit the development and commercial production and sale of avexitide, AMX0035 or any other current or future product candidates, which could harm our business, financial condition, results of operations and prospects.
We may not be able to initiate or continue clinical trials for avexitide, AMX0035 or any other current or future product candidates if we are unable to locate and enroll a sufficient number of eligible patients to participate in these trials to such trial’s conclusion as required by the FDA or other comparable foreign regulatory authorities.
We may not be able to initiate or continue clinical trials for avexitide, AMX0035, AMX0114 or any other current or future product candidates if we are unable to locate and enroll a sufficient number of eligible patients to participate in these trials to such trial’s conclusion as required by the FDA or other comparable foreign regulatory authorities.
Results of our preclinical studies or clinical trials could reveal a high and unacceptable severity and prevalence of side effects or unexpected characteristics. In clinical trials to date of avexitide, avexitide was generally well-tolerated. The most common AEs were injection site bruising, headache, and nausea; these occurred more often with placebo than either avexitide dose.
Results of our 45 preclinical studies or clinical trials could reveal a high and unacceptable severity and prevalence of side effects or unexpected characteristics. In clinical trials to date of avexitide, avexitide was generally well-tolerated. The most common AEs were injection site bruising, headache, and nausea; these occurred more often with placebo than either avexitide dose.
Our consultants and advisors may be employed by other entities and may have commitments under consulting or advisory contracts with those entities that may limit their availability to us. If we are unable to continue to attract and retain highly qualified personnel, our ability to develop avexitide, AMX0035 or any other current or future product candidates will be limited.
Our consultants and advisors may be employed by other entities and may have commitments under consulting or advisory contracts with those entities that may limit their availability to us. If we are unable to continue to attract and retain highly qualified personnel, our ability to develop avexitide, AMX0035, AMX0114 or any other current or future product candidates will be limited.
However, based on the market value of our common stock that was held by non-affiliates as of June 30, 2024, we became an accelerated filer, rather than a large accelerated filer, and we regained smaller reporting company status effective as of December 31, 2024 and have been able to avail ourselves of the reduced disclosure requirements.
Based on the market value of our common stock that was held by non-affiliates as of June 30, 2024, we became an accelerated filer, rather than a large accelerated filer, and we regained smaller reporting company status effective as of December 31, 2024 and have been able to avail ourselves of the reduced disclosure requirements.
If we are unable to do so, we may have to curtail the development of the product candidate for which we are seeking to collaborate, reduce or delay its development program or 54 one or more of our other development programs or activities, delay its potential commercialization or reduce the scope of any sales or marketing activities, or increase our expenditures and undertake development or future commercialization activities at our own expense.
If we are unable to do so, we may have to curtail the development of the product candidate for which we are seeking to collaborate, reduce or delay its development program or one or more of our other development programs or activities, delay its potential commercialization or reduce the scope of any sales or marketing activities, or increase our expenditures and undertake development or future commercialization activities at our own expense.
We also seek to preserve the integrity and confidentiality of 70 our confidential proprietary information by maintaining physical security of our premises and physical and electronic security of our IT systems, but it is possible that these security measures could be breached. In addition, courts outside the U.S. are sometimes less willing to protect trade secrets.
We also seek to preserve the integrity and confidentiality of our confidential proprietary information by maintaining physical security of our premises and physical and electronic security of our IT systems, but it is possible that these security measures could be breached. In addition, courts outside the U.S. are sometimes less willing to protect trade secrets.
It is possible that even if avexitide, AMX0035 or any other current or future product candidate has a beneficial effect, that effect will not be detected during clinical evaluation as a result of one or more of a variety of factors, including the 38 size, duration, design, measurements, conduct or analysis of our clinical trials.
It is possible that even if avexitide, AMX0035 or any other current or future product candidate has a beneficial effect, that effect will not be detected during clinical evaluation as a result of one or more of a variety of factors, including the size, duration, design, measurements, conduct or analysis of our clinical trials.
If we are unable to gain or continue to access rights to these active ingredients prior to conducting preclinical toxicology studies intended to support clinical trials, we may need to develop alternate product candidates from these programs by either accessing or developing alternate active ingredients, resulting in increased development costs and delays in commercialization of these product candidates.
If we are unable to gain or continue to access rights to these active ingredients prior to conducting preclinical toxicology studies intended to support clinical trials, we may need to develop alternate product candidates from these 59 programs by either accessing or developing alternate active ingredients, resulting in increased development costs and delays in commercialization of these product candidates.
Delays or failures in planned patient enrollment or retention may result in increased costs, program delays or both, which could have a harmful effect on our ability to develop AMX0035 in Wolfram syndrome, PSP and additional indications, avexitide and any other current or future product candidates, or could render further development impossible.
Delays or failures in planned patient enrollment or retention may result in increased costs, program delays or both, which could have a harmful effect on our ability to develop AMX0035 in Wolfram syndrome and additional indications, avexitide and any other current or future product candidates, or could render further development impossible.
If we expand our presence outside of the U.S., it will require us to dedicate additional resources to comply with these laws, and these laws may preclude us from 52 developing, manufacturing, or selling certain products and product candidates outside of the U.S., which could limit our growth potential and increase our development costs.
If we expand our presence outside of the U.S., it will require us to dedicate additional resources to comply with these laws, and these laws may preclude us from developing, manufacturing, or selling certain products and product candidates outside of the U.S., which could limit our growth potential and increase our development costs.
In the event of contamination or injury resulting from the use or disposal of our hazardous materials, we could be held liable for any resulting damages, and any liability could exceed our resources. We also could incur significant costs associated with civil or criminal fines and penalties for failure to comply with such laws and regulations.
In the event of contamination or injury resulting from the use or disposal of our hazardous materials, we could be 54 held liable for any resulting damages, and any liability could exceed our resources. We also could incur significant costs associated with civil or criminal fines and penalties for failure to comply with such laws and regulations.
Opposition or cancellation proceedings may be filed against our trademarks, and our trademarks may not survive such proceedings. Moreover, any name we propose to use for our products in the U.S. must be approved by the FDA, regardless of whether we have registered it, or applied to register it, as a trademark.
Opposition or 77 cancellation proceedings may be filed against our trademarks, and our trademarks may not survive such proceedings. Moreover, any name we propose to use for our products in the U.S. must be approved by the FDA, regardless of whether we have registered it, or applied to register it, as a trademark.
These U.S. federal research and development tax credit and U.S. state carryforwards could begin to expire if unused in 2042 and 2035, respectively. Utilization of all NOL and research and development tax credit carryforwards is conditioned upon us generating U.S. federal and state taxable income. Ownership changes occurred in the years ended December 31, 2016 and 2023.
These U.S. federal research and development tax credit and U.S. state carryforwards could begin to expire if unused in 2042 and 2035, respectively. Utilization of all NOL and research and development tax credit carryforwards is conditioned upon us generating U.S. federal and state taxable income. 90 Ownership changes occurred in the years ended December 31, 2016 and 2023.
Supreme Court’s July 2024 decision to overturn prior established case law giving deference to regulatory agencies’ interpretations of ambiguous statutory language has introduced uncertainty regarding the extent to which FDA’s regulations, policies, and decisions may become subject to increasing legal challenges, delays, and/or changes.
Supreme Court’s July 2024 decision to overturn prior established case law giving deference to regulatory agencies’ 39 interpretations of ambiguous statutory language has introduced uncertainty regarding the extent to which the FDA’s regulations, policies, and decisions may become subject to increasing legal challenges, delays, and/or changes.
In some countries, including Canada and certain Member States of the EU, the pricing of prescription drugs is, in part, subject to governmental control. Additional countries may adopt similar approaches to the pricing of prescription drugs. In 62 such countries, pricing negotiations with governmental authorities can take considerable time after receipt of regulatory approval for a product.
In some countries, including Canada and certain Member States of the EU, the pricing of prescription drugs is, in part, subject to governmental control. Additional countries may adopt similar approaches to the pricing of prescription drugs. In such countries, pricing negotiations with governmental authorities can take considerable time after receipt of regulatory approval for a product.
Regardless of whether we have 63 complied with the law, a government investigation, including of any business partners, vendors or charitable foundations, could impact our business practices, harm our reputation, divert the attention of management, increase our expenses, and reduce the availability of foundation support for our patients who need assistance.
Regardless of whether we have complied with the law, a government investigation, including of any business partners, vendors or charitable foundations, could impact our business practices, harm our reputation, divert the attention of management, increase our expenses, and reduce the availability of foundation support for our patients who need assistance.
Neither can we make assurances as to the scope of any claims that may issue from our pending and future patent applications nor to the outcome of any proceedings by any potential third parties that could challenge the patentability, validity or enforceability of our patents and patent applications in the U.S. or 69 foreign jurisdictions.
Neither can we make assurances as to the scope of any claims that may issue from our pending and future patent applications nor to the outcome of any proceedings by any potential third parties that could challenge the patentability, validity or enforceability of our patents and patent applications in the U.S. or foreign jurisdictions.
These agreements typically limit the rights of the third parties to use or disclose our confidential information, including our trade secrets. However, current or former employees, consultants, contractors and advisers may unintentionally or willfully disclose our confidential information to competitors, and confidentiality agreements may not provide an adequate remedy in the event of unauthorized disclosure of confidential information.
These agreements 78 typically limit the rights of the third parties to use or disclose our confidential information, including our trade secrets. However, current or former employees, consultants, contractors and advisers may unintentionally or willfully disclose our confidential information to competitors, and confidentiality agreements may not provide an adequate remedy in the event of unauthorized disclosure of confidential information.
We, or any future partners, collaborators, or licensees, may fail to identify patentable aspects of inventions made in the course of development and commercialization activities before it is too late to obtain patent protection on them. Therefore, we may miss potential opportunities to strengthen our patent position.
We, or any current or future partners, collaborators, or licensees, may fail to identify patentable aspects of inventions made in the course of development and commercialization activities before it is too late to obtain patent protection on them. Therefore, we may miss potential opportunities to strengthen our patent position.
If one or more of these analysts ceases research coverage of us or fails to regularly publish reports on us, we could lose visibility in the financial markets, which in turn could cause our stock price or trading volume to decline. 89 Item 1B. Unresolved Staff Comments. None.
If one or more of these analysts ceases research coverage of us or fails to regularly publish reports on us, we could lose visibility in the financial markets, which in turn could cause our stock price or trading volume to decline. Item 1B. Unresolved Staff Comments. None.
The data exclusivity, if granted, prevents generic or biosimilar applicants from 71 referencing the innovator’s preclinical and clinical trial data contained in the dossier of the reference product when applying for a generic or biosimilar marketing authorization, for a period of eight years from the date on which the reference product was first authorized in the EU.
The data exclusivity, if granted, prevents generic or biosimilar applicants from referencing the innovator’s preclinical and clinical trial data contained in the dossier of the reference product when applying for a generic or biosimilar marketing authorization, for a period of eight years from the date on which the reference product was first authorized in the EU.
Efforts to do so may not result in the actual acquisition or license of a particular product candidate, and, if 46 acquired, may results in extensive diligence and preparation efforts, each of which may potentially result in a diversion of our management’s time and the expenditure of our resources with no resulting benefit.
Efforts to do so may not result in the actual acquisition or license of a particular product candidate, and, if acquired, may results in extensive diligence and preparation efforts, each of which may potentially result in a diversion of our management’s time and the expenditure of our resources with no resulting benefit.
For example, even though AMX0035 is entitled to orphan drug exclusivity, that exclusivity may not prevent the approval of TURSO by the FDA or other regulatory authorities as a monotherapy treatment for Wolfram syndrome if those regulatory agencies determine that TURSO is a different drug product from AMX0035.
For example, even though AMX0035 is entitled to orphan drug exclusivity, that exclusivity may not 50 prevent the approval of TURSO by the FDA or other regulatory authorities as a monotherapy treatment for Wolfram syndrome if those regulatory agencies determine that TURSO is a different drug product from AMX0035.
For a patent filed March 16, 2013 or later, a petition for post-grant review can be filed by a third party in a nine-month window from issuance of the patent. A petition for inter partes review can be filed immediately following the issuance of a patent if the patent has an effective filing date prior to March 16, 2013.
For a patent filed March 16, 2013 or later, a petition for post-grant review can be filed by a third party in a nine-month window from issuance of the patent. A petition for inter partes review can be filed 72 immediately following the issuance of a patent if the patent has an effective filing date prior to March 16, 2013.
If the actual number of patients with these diseases is smaller than we anticipate, we may encounter difficulties in enrolling patients in our clinical trials, thereby delaying or preventing development and approval of avexitide, AMX0035 or any other current or future product candidates.
If the actual number of patients with these diseases is smaller than we anticipate, we may encounter difficulties in enrolling patients in our clinical trials, thereby delaying or preventing development and approval of avexitide, AMX0035, AMX0114 or any other current or future product candidates.
However, even if an innovative medicinal product gains the prescribed period of data exclusivity, another company may market another version of the product if such company obtained a marketing authorization based on an application with a complete and independent data package of pharmaceutical tests, preclinical tests and clinical trials.
However, even if an innovative medicinal product gains the prescribed period of data exclusivity, another company may market another version of 74 the product if such company obtained a marketing authorization based on an application with a complete and independent data package of pharmaceutical tests, preclinical tests and clinical trials.
Although the length and impact of the ongoing military conflict is highly unpredictable, the conflict in Ukraine has led to market disruptions, including significant volatility in commodity prices, credit and capital markets, as well as supply chain interruptions, which contributed to record inflation globally.
Although the length and impact of the ongoing military conflict is highly unpredictable, the conflict in Ukraine has led to market disruptions, including significant volatility in commodity prices, credit and capital 82 markets, as well as supply chain interruptions, which contributed to record inflation globally.
We and any future 31 collaborators may never succeed in these activities and, even if we do, or any future collaborators do, we may never generate revenues that are large enough for us to achieve profitability. Even if we do achieve profitability, we may not be able to sustain or increase profitability on a quarterly or annual basis.
We and any future collaborators may never succeed in these activities and, even if we do, or any future collaborators do, we may never generate revenues that are large enough for us to achieve profitability. Even if we do achieve profitability, we may not be able to sustain or increase profitability on a quarterly or annual basis.
Risks Related to Commercialization of Avexitide, AMX0035 or Future Product Candidates The markets for avexitide for PBH, and congenital HI, for AMX0035 for Wolfram syndrome, PSP and other neurodegenerative diseases, and for any other product candidates we are currently developing or may in the future develop or acquire may be smaller than we expect.
Risks Related to Commercialization of Avexitide, AMX0035 or Future Product Candidates The markets for avexitide for PBH, and Congenital HI, for AMX0035 for Wolfram syndrome and other neurodegenerative diseases, and for any other product candidates we are currently developing or may in the future develop or acquire may be smaller than we expect.
If we continue to suffer losses as we have in the past, prior to the commercialization of RELYVRIO and ALBRIOZA, investors may not receive any return on their investment and may lose their entire investment. Our quarterly and annual operating results may fluctuate in the future.
If we continue to suffer losses as we have in the past, prior to the commercialization of RELYVRIO and ALBRIOZA, investors may not receive any return on their investment and may lose their entire investment. 32 Our quarterly and annual operating results may fluctuate in the future.
This could result in our own products being removed from the market or being less commercially successful. Finally, clinical trials of avexitide and AMX0035 are conducted in carefully defined sets of patients who have agreed to enter into clinical trials.
This could result in our own products being removed from the market or being less commercially successful. Finally, clinical trials of avexitide, AMX0035, and AMX0114 are conducted in carefully defined sets of patients who have agreed to enter into clinical trials.
Demand for expanded access to AMX0035 could negatively affect our reputation and harm our business. We are developing AMX0035 for the treatment of Wolfram syndrome, PSP and other potential future indications for which there are currently limited or no available therapeutic options.
Demand for expanded access to AMX0035 could negatively affect our reputation and harm our business. We are developing AMX0035 for the treatment of Wolfram syndrome and other potential future indications for which there are currently limited or no available therapeutic options.
In addition, our failure to demonstrate positive results in our clinical trials in any indication for which we are developing our current product candidates, or to satisfy other regulatory requirements, could adversely affect our development efforts for avexitide, AMX0035 in other indications, or for AMX0114.
In addition, our failure to demonstrate positive results in our clinical trials in any indication for which we are developing our current product candidates, or to satisfy other regulatory requirements, could adversely affect our development efforts for avexitide, AMX0035 in other indications, AMX0114, or AMX0318.
This could delay completion 43 of clinical trials, require the repetition of one or more clinical trials, increase clinical trial costs, delay approval of avexitide, AMX0035 or any other current or future product candidates and jeopardize our ability to commence sales and generate revenue.
This could delay completion of clinical trials, require the repetition of one or more clinical trials, increase clinical trial costs, delay approval of avexitide, AMX0035 or any other current or future product candidates and jeopardize our ability to commence sales and generate revenue.
For example, we received priority review for AMX0035 for the treatment of ALS, and we may in the future request Priority Review Designation for any future product candidates, however, we cannot assume that any application for future indications of avexitide, AMX0035 or any other product candidate we may develop will meet 49 the criteria for that designation.
For example, we received priority review for AMX0035 for the treatment of ALS, and we may in the future request Priority Review Designation for any future product candidates, however, we cannot assume that any application for future indications of avexitide, AMX0035 or any other product candidate we may develop will meet the criteria for that designation.
If our trademarks and trade names are not adequately protected, then we may not be able to build name recognition in our trademarks and our business may be adversely affected. 74 Our trademarks or trade names may be challenged, infringed, circumvented or declared generic or determined to be infringing on other marks.
If our trademarks and trade names are not adequately protected, then we may not be able to build name recognition in our trademarks and our business may be adversely affected. Our trademarks or trade names may be challenged, infringed, circumvented or declared generic or determined to be infringing on other marks.
We plan to conduct several clinical trials for AMX0035 in parallel over the next several years, including clinical trials in patients with Wolfram syndrome, PSP and other indications, which may make our decision as to which indication to prioritize more difficult.
We plan to conduct several clinical trials for AMX0035 in parallel over the next several years, including clinical trials in patients with Wolfram syndrome and other indications, which may make our decision as to which indication to prioritize more difficult.
Product liability claims may be brought against us or our partners by participants enrolled in our clinical trials, patients, health care providers, pharmaceutical companies, our collaborators or others using, administering or selling any of our future approved products.
Product liability claims may be brought 52 against us or our partners by participants enrolled in our clinical trials, patients, health care providers, pharmaceutical companies, our collaborators or others using, administering or selling any of our future approved products.
Moreover, we might obtain marketing approval for a product in a particular country, but then be subject to price regulations that delay or might even prevent our commercial launch of the product, 61 possibly for lengthy periods of time.
Moreover, we might obtain marketing approval for a product in a particular country, but then be subject to price regulations that delay or might even prevent our commercial launch of the product, possibly for lengthy periods of time.
With respect to protection of our intellectual property rights in avexitide, our acquisition of that product candidate from Eiger includes acquisition of all of Eiger’s owned and co-owned patents and applications directed to 66 avexitide, as well as assuming Eiger’s licenses to patents and applications directed to avexitide and owned and co-owned by other entities.
With respect to protection of our intellectual property rights in avexitide, our acquisition of that product candidate from Eiger includes acquisition of all of Eiger’s owned and co-owned patents and applications directed to avexitide, as well as assuming Eiger’s licenses to patents and applications directed to avexitide and owned and co-owned by other entities.
Sanctions imposed by the U.S. and other countries in response to such conflicts may also continue to adversely impact the financial markets and the global economy, and any economic countermeasures by the affected countries or others could exacerbate market and economic instability.
Sanctions imposed by the U.S. and other countries in response to such conflicts may also continue to adversely impact the financial markets and the global economy, and any economic countermeasures by the affected countries or others could exacerbate market and economic 84 instability.
Any product candidates we 41 develop may not be effective, may be only moderately effective, or may prove to have undesirable or unintended side effects, toxicities or other characteristics that may preclude our obtaining marketing approval or prevent or limit commercial use.
Any product candidates we develop may not be effective, may be only moderately effective, or may prove to have undesirable or unintended side effects, toxicities or other characteristics that may preclude our obtaining marketing approval or prevent or limit commercial use.
We cannot provide any assurances that any of our patents have, or that any of our pending owned patent applications that mature into issued patents will include claims with a scope sufficient to protect our proprietary therapeutics or otherwise provide any competitive advantage.
We cannot provide any assurances that any of our patents have, or that any of our pending owned patent applications that mature into issued patents will include claims with a 69 scope sufficient to protect our proprietary therapeutics or otherwise provide any competitive advantage.
Replacing executive officers or other key employees may be difficult and may take an extended period of time because of the limited number of individuals in our industry with the breadth of skills and experience required to develop, gain regulatory approval of and commercialize products successfully. 79 Competition to hire from this limited pool is intense, and we may be unable to hire, train, retain or motivate these additional key employees on acceptable terms given the competition among numerous pharmaceutical and biotechnology companies for similar personnel.
Replacing executive officers or other key employees may be difficult and may take an extended period of time because of the limited number of individuals in our industry with the breadth of skills and experience required to develop, gain regulatory approval of and commercialize products successfully. 81 Competition to hire from this limited pool is intense, and we may be unable to hire, train, retain or motivate these additional key employees on acceptable terms given the competition among numerous pharmaceutical and biotechnology companies for similar personnel.
The FDA has broad discretion whether or not to grant this designation, so even if we believe a particular product candidate is eligible for this designation, we cannot assure you that the FDA would decide to grant it.
The FDA has broad discretion whether or not to grant this designation, so even if we believe a particular product candidate is eligible for this designation, we cannot assure you that 51 the FDA would decide to grant it.
Publications of discoveries in the scientific literature often lag behind the actual discoveries, and patent applications in the U.S. and other jurisdictions are not published until 18 months after filing, or in 67 some cases not at all.
Publications of discoveries in the scientific literature often lag behind the actual discoveries, and patent applications in the U.S. and other jurisdictions are not published until 18 months after filing, or in some cases not at all.
Moreover, such proceedings could put our patents at risk of being invalidated or 72 held unenforceable, or interpreted narrowly, and our pending patent applications at risk of not issuing, and could provoke third parties to assert claims against us.
Moreover, such proceedings could put our patents at risk of being invalidated or held unenforceable, or interpreted narrowly, and our pending patent applications at risk of not issuing, and could provoke third parties to assert claims against us.
Even if we are successful in these 73 proceedings, we may incur substantial costs and the time and attention of our management and scientific personnel could be diverted in pursuing these proceedings, which could significantly harm our business and operating results.
Even if we are successful in these proceedings, we may incur substantial costs and the time and attention of our management and scientific personnel could be diverted in pursuing these proceedings, which could significantly harm our business and operating results.
We rely on third parties for research and development work, and expect to rely on third parties for future manufacturing of our proprietary product candidate, avexitide, AMX0035, AMX0114, and any other current or future product candidates. We also expect to collaborate with third parties on the development of avexitide, 75 AMX0035, AMX0114, and any other current or future product candidates.
We rely on third parties for research and development work, and expect to rely on third parties for future manufacturing of our proprietary product candidate, avexitide, AMX0035, AMX0114, and any other current or future product candidates. We also expect to collaborate with third parties on the development of avexitide, AMX0035, AMX0114, and any other current or future product candidates.
The future regulatory and commercial success of avexitide, AMX0035 or any other current or future product candidates are subject to a number of risks, including the following: • successful completion of preclinical studies and clinical trials; • successful patient enrollment in clinical trials; • positive data from our preclinical studies and clinical trials that supports an acceptable risk-benefit profile of avexitide, AMX0035 or any other current or future product candidates in the intended populations; • satisfaction of applicable regulatory requirements, including to satisfy applicable rules governing fixed dose combination products, as applicable; 35 • the interpretation of our preclinical and clinical data by regulatory authorities to support marketing approvals; • potential unforeseen safety issues or adverse side effects; • receipt and maintenance of marketing approvals from applicable regulatory authorities, including with any expected NCE and new clinical investigation data exclusivity and orphan drug market exclusivity, as applicable; • receipt and maintenance of designations from applicable regulatory authorities, including breakthrough designation for avexitide and orphan designation for avexitide and AMX0035; • obtaining and maintaining patent and trade secret protection and regulatory exclusivity for avexitide, AMX0035 or any other current or future product candidates; • making arrangements with third-party manufacturers, or establishing manufacturing capabilities, for both clinical and commercial supplies of avexitide, AMX0035 or any other current or future product candidates; • entry into collaborations to further the development of avexitide, AMX0035 or any other current or future product candidates; • establishing sales, marketing and distribution capabilities and launching commercial sales of our products, if and when approved, whether alone or in collaboration with others; • acceptance of avexitide, AMX0035 or any other products, if and when approved, by patients, the medical community and third-party payors; • appropriately identifying patients with the diseases targeted by avexitide, AMX0035 or any other current or future product candidates and accurately estimating the size of applicable patient populations or disease prevalence; • obtaining and maintaining third-party coverage and adequate reimbursement; • maintaining a continued acceptable safety profile of products following any approval; • effectively competing with other drugs or therapies; • ensuring that we promote and distribute our products consistent with all applicable healthcare laws; and • enforcing and defending intellectual property rights and claims.
The future regulatory and commercial success of avexitide, AMX0035, AMX0114, AMX0318 or any other current or future product candidates are subject to a number of risks, including the following: • successful completion of preclinical studies and clinical trials; • successful patient enrollment in clinical trials; • positive data from our preclinical studies and clinical trials that supports an acceptable risk-benefit profile of avexitide, AMX0035 or any other current or future product candidates in the intended populations; • satisfaction of applicable regulatory requirements, including to satisfy applicable rules governing fixed dose combination products, as applicable; • the interpretation of our preclinical and clinical data by regulatory authorities to support marketing approvals; • potential unforeseen safety issues or adverse side effects; • receipt and maintenance of marketing approvals from applicable regulatory authorities, including with any expected NCE and new clinical investigation data exclusivity and orphan drug market exclusivity, as applicable; • receipt and maintenance of designations from applicable regulatory authorities, including breakthrough designation for avexitide, orphan designation for avexitide and AMX0035, and Fast Track Designation for AMX0114; • obtaining and maintaining patent and trade secret protection and regulatory exclusivity for avexitide, AMX0035 or any other current or future product candidates; • making arrangements with third-party manufacturers, or establishing manufacturing capabilities, for both clinical and commercial supplies of avexitide, AMX0035, AMX0114, AMX0318 or any other current or future product candidates; • entry into collaborations to further the development of avexitide, AMX0035, AMX0114, AMX0318 or any other current or future product candidates; • establishing sales, marketing and distribution capabilities and launching commercial sales of our products, if and when approved, whether alone or in collaboration with others; • acceptance of avexitide, AMX0035 or any other products, if and when approved, by patients, the medical community and third-party payors; • appropriately identifying patients with the diseases targeted by avexitide, AMX0035, AMX0114, AMX0318 or any other current or future product candidates and accurately estimating the size of applicable patient populations or disease prevalence; • obtaining and maintaining third-party coverage and adequate reimbursement; • maintaining a continued acceptable safety profile of products following any approval; • effectively competing with other drugs or therapies; • ensuring that we promote and distribute our products consistent with all applicable healthcare laws; and • enforcing and defending intellectual property rights and claims.
These requirements include submissions of safety and other post-marketing information and reports, registration and listing requirements, requirements relating to manufacturing, quality control, quality assurance and corresponding maintenance of records and documents, requirements regarding the distribution of samples to physicians and recordkeeping.
These requirements include submissions of safety and other post-marketing information and reports, registration and listing requirements, requirements relating to manufacturing, quality control, quality assurance and corresponding maintenance of records and documents, requirements regarding the distribution of samples to physicians and 61 recordkeeping.
Any negative results we may report in clinical trials of avexitide, AMX0035 or any future product candidate may also make it difficult or impossible to recruit and retain patients in other clinical trials of that same product candidate.
Any negative results we may report in clinical trials of avexitide, AMX0035, AMX0114 or any future product candidate may also make it difficult or impossible to recruit and retain patients in other clinical trials of that same product candidate.
If unacceptable or severe side effects arise in the development of avexitide, AMX0035 or any other current or future product candidates, we, the FDA or comparable foreign regulatory authorities, the IRBs, or independent ethics committees at the institutions in which our trials are conducted, or the independent safety monitoring committee could suspend or terminate our clinical trials or regulatory authorities could order us to cease clinical trials or deny approval of avexitide, AMX0035 or any other current or future product candidates for any or all targeted indications.
If unacceptable or severe side effects arise in the development of avexitide, AMX0035, AMX0114, AMX0318 or any other current or future product candidates, we, the FDA or comparable foreign regulatory authorities, the IRBs, or independent ethics committees at the institutions in which our trials are conducted, or the independent safety monitoring committee could suspend or terminate our clinical trials or regulatory authorities could order us to cease clinical trials or deny approval of avexitide, AMX0035, AMX0114, AMX0318 or any other current or future product candidates for any or all targeted indications.
Following the withdrawal of RELYVRIO/ALBRIOZA from the market in the US and Canada, respectively, we do not have any products approved for commercial sale and we will continue to incur significant research and development and other expenses related to clinical development and potential approvals for our current and future product candidates, including for avexitide, AMX0035 in additional indications other than ALS, and for ongoing operations.
Following the withdrawal of RELYVRIO/ALBRIOZA from the market in the US and Canada, respectively, we do not have any products approved for commercial sale and we will continue to incur 31 significant research and development and other expenses related to clinical development and potential approvals for our current and future product candidates, including for avexitide, AMX0035 and AMX0114 in additional indications other than ALS, and for ongoing operations.
If that occurs, we will not be able to, or may be delayed in our efforts to, successfully commercialize avexitide, AMX0035 or any other current or future product candidates.
If that occurs, we will not be able to, or may be delayed in our efforts to, successfully 55 commercialize avexitide, AMX0035 or any other current or future product candidates.
Ongoing third-party data in 37 neurology, specifically within ALS, on our products or other products may influence regulatory decision making, including for fixed-dose combinations.
Ongoing third-party data in neurology, specifically within ALS, on our products or other products may influence regulatory decision making, including for fixed-dose combinations.
The foreign regulatory approval process involves all of the risks associated with FDA approval. We do not have experience in obtaining regulatory approval in international markets outside of Canada.
The foreign regulatory approval process involves all of the risks associated with FDA approval. We do not have experience in obtaining regulatory 49 approval in international markets outside of Canada.

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Item 1C. Cybersecurity

Cybersecurity — threats and controls disclosure

9 edited+1 added−3 removed6 unchanged
Biggest changeWe maintain a Written Information Security Program, or WISP, that defines our organization’s cybersecurity policies and procedures. This covers all aspects of cybersecurity, including but not limited to risk management, third party security assessments, security awareness training, acceptable use, endpoint security, patch management, log management, backup and recovery. We face a number of cybersecurity risks in connection with our business.
Biggest changeThis covers all aspects of cybersecurity, including but not limited to: • risk management; • incident response; • third party security assessments and data protection agreements, required of all vendors that access, store or process our data; • mandatory security awareness and phishing training through digital microlearning assignments; 91 • acceptable use; • endpoint security; • patch management; • log management; and • backup and recovery.
Our IT security team also meets regularly with our Global Privacy Committee, which oversees our Enterprise Data Protection Program, to coordinate on cybersecurity initiatives and strategy related to protection of personal data.
Our IT security team also meets regularly with our Global Privacy Committee, which oversees our Enterprise Data Protection Program, to coordinate on cybersecurity initiatives and strategy related to protection of personal data. 92
The Head of Global ISGA maintains a Certified Information Systems Security Professionals, or CISSP, certification and has more than two decades of IT security management experience. The IT security team is supported by external vendors that provide managed services for network support, security operations and other IT areas as needed.
The Senior Director of ISGA maintains a Certified Information Systems Security Professionals, or CISSP, certification and has more than two decades of IT security management experience. The IT security team is supported by external vendors that provide managed services for network support, security operations and other IT areas as needed.
Senior management is thus kept abreast of the cybersecurity posture and potential risks facing our company. Our cybersecurity incident response process is designed to proactively triage, contain, investigate, mitigate and correct all incidents at the direction of the Head of Global Information Technology.
Senior management is thus kept abreast of the cybersecurity posture and potential risks facing our company. Our cybersecurity incident response process is designed to proactively triage, contain, investigate, mitigate and correct all incidents at the direction of the Senior Vice President of Information Technology.
Our executive leadership team meets with our Head of Global Information Technology, along with other members of our IT security team as needed, to discuss cybersecurity matters, such as the emerging cybersecurity threat landscape, significant developments to our cybersecurity processes, and our cybersecurity risk assessments.
Our executive leadership team meets with our Senior Vice President of Information Technology, along with other members of our IT security team as needed, to discuss cybersecurity matters, such as the emerging cybersecurity threat landscape, significant developments to our cybersecurity processes, and our cybersecurity risk assessments.
The Head of Global ISGA reports to our Head of Global Information Technology. The Head of Global ISGA routinely reports on cybersecurity risks, projects, and initiatives to the Head of Global Information Technology, who regularly reports to executive management and the audit committee on these matters as described above.
The Senior Director of ISGA reports to our Senior Vice President of Information Technology. The Senior Director of ISGA routinely reports on cybersecurity risks, projects, and initiatives to the Senior Vice President of Information Technology, who regularly reports to executive management and the audit committee on these matters as described above.
In an effort to address the threat landscape, we maintain a cybersecurity risk management strategy that is designed to identify, assess, manage, and address cybersecurity threats that may have a material impact on our business.
In an effort to address the threat landscape, we maintain a cybersecurity risk management strategy that is designed to identify, assess, manage, and address cybersecurity threats that may have a material impact on our business. We maintain a Written Information Security Program that defines our organization’s cybersecurity policies and procedures.
Furthermore, significant cybersecurity matters, and strategic risk management decisions are escalated to the Board of Directors, as needed, to provide oversight and guidance on critical cybersecurity issues. 90 Our IT security team, led by the Head of Global Information Security, Governance and Architecture (“Head of Global ISGA”), is responsible for managing and directing the day-to-day information security strategy of the organization, including oversight of our cybersecurity tools , controls and strategies to protect organization assets, networks and data.
Our IT security team, led by the Senior Director of Information Security, Governance and Architecture, or the Senior Director of ISGA, is responsible for managing and directing the day-to-day information security strategy of the organization, including oversight of our cybersecurity tools , controls and strategies to protect organization assets, networks and data.
Critical incidents are assessed for materiality, and escalated to the executive leadership team for awareness, direction and approval as needed.
Critical incidents are assessed for materiality, and escalated to the executive leadership team for awareness, direction and approval as needed. Furthermore, significant cybersecurity matters, and strategic risk management decisions are escalated to the board of directors, as needed, to provide oversight and guidance on critical cybersecurity issues.
Removed
Our cybersecurity risk management strategy includes various policies and components, including cybersecurity assessments, an incident response plan, evaluation of the security practices of our key vendors, and cybersecurity awareness training for our staff.
Added
We face a number of cybersecurity risks in connection with our business.
Removed
We have established a process to review and assess vendors’ security posture and practices prior to their onboarding. Vendors that access, store or process our data are required to respond to a cybersecurity questionnaire and provide applicable security audit reports and certifications.
Removed
Our process also includes contractual requirements to maintain data protection safeguards for vendors that process data on our behalf. We maintain a security awareness training program for employees, which is provided through digital microlearning assignments. We also provide additional mandatory trainings, including phishing training, throughout the year.

Item 2. Properties

Properties — owned and leased real estate

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Biggest changeDetails of our principal properties as of December 31, 2024, are provided below: Property Description Location Square Footage Property Interest Initial Lease Term End Date Office space Cambridge, Massachusetts 8,850 Leased October 2026 Office space Cambridge, Massachusetts 24,400 Leased July 2025 Office space Cambridge, Massachusetts 15,267 Leased December 2030 We believe that our facilities are adequate for our current needs and that suitable additional or substitute space would be available if needed.
Biggest changeDetails of our principal properties as of December 31, 2025, are provided below: Property Description Location Square Footage Property Interest Initial Lease Term End Date Office space Cambridge, Massachusetts 8,850 Leased October 2026 Office space Cambridge, Massachusetts 15,267 Leased December 2030 We believe that our facilities are adequate for our current needs and that suitable additional or substitute space would be available if needed.

Item 3. Legal Proceedings

Legal Proceedings — active lawsuits and investigations

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Biggest changeItem 3. Legal Proceedings. On February 9, 2024, a putative class action lawsuit was filed in the U.S. District Court for the Southern District of New York against us and certain of our current and former officers ( Shih v. Amylyx Pharmaceuticals, Inc., et al. , Case Number 1:24-CV-00988, or the Shih Complaint).
Biggest changeItem 3. Legal Proceedings. On February 9, 2024, a putative class action lawsuit was filed in the U.S. District Court for the Southern District of New York against us and certain of our current and former officers (Shih v. Amylyx Pharmaceuticals, Inc., et al., Case Number 1:24-CV-00988, or the Shih Complaint). Plaintiff filed an amended complaint on June 24, 2024.
District Court for the District of Massachusetts against certain current and former director and officer defendants, or the Individual Defendants, naming us as a nominal defendant ( Jones v. Cohen, et al ., 1:24-CV-12527, or the Derivative Complaint).
District Court for the District of Massachusetts against certain current and former director and officer defendants, or the Individual Defendants, naming us as a nominal defendant (Jones v. Cohen, et al., 1:24-CV-12527, or the Jones Derivative Complaint).
The Derivative Complaint seeks unspecified damages to be awarded to the Company along with interest, restitution, unspecified corporate governance and internal procedural reforms and improvements, and plaintiff's attorneys' fees and costs.
The Jones Derivative Complaint seeks unspecified damages to be awarded to the Company along with interest, restitution, unspecified corporate governance and internal procedural reforms and improvements, and plaintiff's attorneys' fees and costs.
At this time, an estimate of the impact, if any, of the claims made in the Shih Complaint and Derivative Complaint cannot be made. 91 Item 4. Mine Safety Disclosures. Not Applicable. 92 PART II
At this time, an estimate of the impact, if any, of the claims made in the Shih Complaint and Derivative Complaints cannot be made. Item 4. Mine Safety Disclosures. Not Applicable. 93 PART II
Plaintiff filed an amended complaint on June 24, 2024. The Shih Complaint asserts a claim against all defendants for alleged violations of Section 10(b) of the Exchange Act and Rule 10b-5 promulgated thereunder and a claim under Section 20(a) against certain current and former officers as alleged controlling persons.
The Shih Complaint asserts a claim against all defendants for alleged violations of Section 10(b) of the Exchange Act and Rule 10b-5 promulgated thereunder and a claim under Section 20(a) against certain current and former officers as alleged controlling persons.
On October 31, 2024, the Court entered an order staying the action until the earlier of the dismissal of the Shih Complaint with prejudice, including the exhaustion of all appeals, or defendants file an answer to the Shih Complaint. We intend to defend against the Shih Complaint and Derivative Complaint vigorously.
On October 31, 2024, the Court entered an order staying the action until the earlier of the dismissal of the Shih Complaint with prejudice, including the exhaustion of all appeals, or defendants file an answer to the Shih Complaint.
Removed
Plaintiff filed his opposition to defendants’ motion to dismiss on October 21, 2024 and defendants filed their reply brief in further support of their motion to dismiss on November 20, 2024. In addition to the Shih Complaint, on October 2, 2024, a derivative complaint was filed in the U.S.
Added
On September 30, 2025, the Court issued an order finding that the majority of the alleged misstatements are inactionable, but ultimately denied the motion to dismiss. The Company filed an answer on October 30, 2025.
Added
The parties have agreed to participate in a confidential mediation, currently scheduled for March 12, 2026, in an attempt to resolve this action, and will provide a status update to the court by April 12, 2026. In addition to the Shih Complaint, on October 2, 2024, a derivative complaint was filed in the U.S.
Added
On July 2, 2025, a second derivative complaint was filed in the Court against certain current and former directors and officer defendants, naming the Company as nominal defendant (Hassine v. Cohen, et al., 1:25-CV-11879, or the Hassine Derivative Complaint and, together with the Jones Derivative Complaint, the Derivative Complaints).
Added
The substantive allegations mirror those of the Shih Complaint but also include claims for alleged violations of Sections 14(a), 10(b), and 21D of the Exchange Act, breach of fiduciary duty, and certain other common law claims.
Added
The Hassine Derivative Complaint seeks unspecified damages to be awarded to the Company along with interest, costs, and attorneys’ fees, restitution, and certain corporate governance and internal procedural reforms and improvements.
Added
On July 16, 2025, the parties to both Derivative Complaints moved the Court to consolidate the Hassine Derivative Complaint with the Jones Derivative Complaint and stay the action according to the terms of the previously-entered stay of the Jones Derivative Complaint. The Court approved the motion on July 22, 2025.
Added
Due to the above-referenced mediation currently scheduled for March 12, 2026, the previously-entered stay has been extended through April 30, 2026, at which point the parties will determine whether to enter a proposed case schedule or further extend the stay. We intend to defend against the Shih Complaint and Derivative Complaints vigorously.

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

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Biggest changeHolders of Record As of February 28, 2025, we had approximately 17 holders of record of our common stock. Certain shares are held in “street” name and accordingly, the number of beneficial owners of such shares is not known or included in the foregoing number.
Biggest changeHolders of Record As of February 23, 2026, we had approximately 16 holders of record of our common stock. Certain shares are held in “street” name and accordingly, the number of beneficial owners of such shares is not known or included in the foregoing number.
Purchases of Equity Securities by the Issuer and Affiliated Purchasers We did not purchase any of our registered equity during the period covered by this Annual Report. Unregistered Sales of Securities During the year ended December 31, 2024, we did not issue or sell any unregistered securities. Item 6. [Reserved ] 93
Purchases of Equity Securities by the Issuer and Affiliated Purchasers We did not purchase any of our registered equity during the period covered by this Annual Report. Unregistered Sales of Securities During the year ended December 31, 2025, we did not issue or sell any unregistered securities. Item 6. [Reserved ] 94

Item 7. Management's Discussion & Analysis

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

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Biggest changeAs a result, we don’t expect to incur material income taxes for the foreseeable future. 97 Results of Operations Comparison of the Years Ended December 31, 2024 and 2023 The following table summarizes our results of operations for the years ended December 31, 2024 and 2023: Year Ended December 31, 2024 2023 $ Change % Change (in thousands) Product revenue, net $ 87,371 $ 380,786 $ (293,415 ) (77 )% Operating expenses: Cost of sales 5,953 25,441 (19,488 ) (77 )% Cost of sales - inventory impairment and loss on firm purchase commitments 118,680 — 118,680 *NM Acquired in-process research and development 36,203 — 36,203 *NM Research and development 104,084 128,187 (24,103 ) (19 )% Selling, general and administrative 114,331 188,356 (74,025 ) (39 )% Restructuring expenses 22,851 — 22,851 *NM Total operating expenses 402,102 341,984 60,118 18 % (Loss) income from operations (314,731 ) 38,802 (353,533 ) (911 )% Other income, net: Interest income 13,809 16,155 (2,346 ) (15 )% Other expense, net (1,214 ) (660 ) (554 ) 84 % Total other income, net 12,595 15,495 (2,900 ) (19 )% (Loss) income before income taxes (302,136 ) 54,297 (356,433 ) (656 )% (Benefit) provision for income taxes (393 ) 5,026 (5,419 ) (108 )% Net (loss) income $ (301,743 ) $ 49,271 $ (351,014 ) (712 )% * NM - not meaningful Product revenue, net Product revenue, net was $87.4 million for the year ended December 31, 2024, compared to $380.8 million for the year ended December 31, 2023.
Biggest changeResults of Operations Comparison of the Years Ended December 31, 2025 and 2024 The following table summarizes our results of operations for the years ended December 31, 2025 and 2024: Year Ended December 31, 2025 2024 $ Change % Change (in thousands) Product revenue, net $ — $ 87,371 $ (87,371 ) (100 )% Operating expenses: Cost of sales — 5,953 (5,953 ) (100 )% Cost of sales - inventory impairment and loss on firm purchase commitments — 118,680 (118,680 ) (100 )% Acquired in-process research and development — 36,203 (36,203 ) (100 )% Research and development 90,404 104,084 (13,680 ) (13 )% Selling, general and administrative 62,887 114,331 (51,444 ) (45 )% Restructuring expenses — 22,851 (22,851 ) (100 )% Total operating expenses 153,291 402,102 (248,811 ) (62 )% Loss from operations (153,291 ) (314,731 ) 161,440 (51 )% Other income, net: Interest income 9,302 13,809 (4,507 ) (33 )% Other expense, net (700 ) (1,214 ) 514 (42 )% Total other income, net 8,602 12,595 (3,993 ) (32 )% Loss before income taxes (144,689 ) (302,136 ) 157,447 (52 )% Provision (benefit) for income taxes 46 (393 ) 439 (112 )% Net loss $ (144,735 ) $ (301,743 ) $ 157,008 (52 )% 97 Product revenue, net and Cost of sales In April 2024, we announced we had started a process with the FDA and Health Canada to voluntarily discontinue the marketing authorizations for RELYVRIO®/ALBRIOZA™ (sodium phenylbutyrate and taurursodiol [also known as ursodoxicoltaurine]; also known as AMX0035) for the treatment of ALS and remove the product from the market in the U.S. and Canada, or the “RELYVRIO®/ALBRIOZA™ Discontinuation.
Overview We are a clinical-stage pharmaceutical company with a mission to develop novel therapies for communities with high unmet medical needs. We have preclinical and clinical development programs underway in neurodegenerative diseases and endocrine conditions.
Overview We are a clinical-stage pharmaceutical company with a mission to develop novel therapies for communities with high unmet medical needs. We have preclinical and clinical development programs underway in endocrine conditions and neurodegenerative diseases.
The successful development and commercialization of avexitide, AMX0035 and any other current or future product candidates is highly uncertain, due to the numerous risks and uncertainties associated with product development and commercialization, including the following: • the timing and progress of preclinical and clinical development activities; • the number and scope of preclinical and clinical trials for separate indications we decide to pursue; • raising additional funds, if necessary; • the progress of the development efforts of parties with whom we may enter into collaboration arrangements; • our ability to maintain our current development activities and to establish new ones; • our ability to establish new licensing or collaboration arrangements; 96 • the successful initiation and completion of clinical trials with safety, tolerability and efficacy profiles that are satisfactory to the FDA or any other comparable foreign regulatory authority; • the availability of drug substance and drug product for use in production of avexitide, AMX0035 or other product candidates; • establishing and maintaining agreements with third-party manufacturers for clinical supply for our clinical trials; • our ability to obtain and maintain patents, trade secret protection and regulatory exclusivity, both in the U.S. and internationally; • our ability to protect our rights in our intellectual property portfolio; • obtaining and maintaining third-party insurance coverage and adequate reimbursement in the future for any approved products; • the acceptance of our products and product candidates, if approved, by patients, the medical community and third-party payors; • competition with other products; and • a continued acceptable safety profile of our therapies in pre-approval market access programs or in commercial access following approval.
The successful development and commercialization of avexitide, AMX0035, AMX0114, AMX0318 and any other current or future product candidates is highly uncertain, due to the numerous risks and uncertainties associated with product development and commercialization, including the following: • the timing and progress of preclinical and clinical development activities; • the number and scope of preclinical and clinical trials for separate indications we decide to pursue; • raising additional funds, if necessary; • the progress of the development efforts of parties with whom we may enter into collaboration arrangements; • our ability to maintain our current development activities and to establish new ones; • our ability to establish new licensing or collaboration arrangements; • the successful initiation and completion of clinical trials with safety, tolerability and efficacy profiles that are satisfactory to the FDA or any other comparable foreign regulatory authority; • the availability of drug substance and drug product for use in production of avexitide, AMX0035 or other product candidates; • establishing and maintaining agreements with third-party manufacturers for clinical supply for our clinical trials; • our ability to obtain and maintain patents, trade secret protection and regulatory exclusivity, both in the U.S. and internationally; • our ability to protect our rights in our intellectual property portfolio; • obtaining and maintaining third-party insurance coverage and adequate reimbursement in the future for any approved products; • the acceptance of our products and product candidates, if approved, by patients, the medical community and third-party payors; 96 • competition with other products; and • a continued acceptable safety profile of our therapies in pre-approval market access programs or in commercial access following approval.
The majority of our service providers invoice us in arrears for services performed, on a pre-determined schedule or when contractual milestones are met; however, some require advance payments. We make estimates of our accrued expenses as of each balance sheet date in the consolidated financial statements based on facts and circumstances known to us at that time.
The majority of our service providers invoice us in arrears for services performed, on a pre-determined schedule or when contractual milestones are met; however, some require advance payments. We make estimates of our accrued expenses as of 102 each balance sheet date in the consolidated financial statements based on facts and circumstances known to us at that time.
This process involves reviewing open contracts and purchase orders, communicating 103 with our personnel to identify services that have been performed on our behalf and estimating the level of service performed and the associated cost incurred for the service when we have not yet been invoiced or otherwise notified of actual costs.
This process involves reviewing open contracts and purchase orders, communicating with our personnel to identify services that have been performed on our behalf and estimating the level of service performed and the associated cost incurred for the service when we have not yet been invoiced or otherwise notified of actual costs.
To date, there have not been any material adjustments to our prior estimates of accrued research and development expenses. Recently Issued Accounting Pronouncements A description of recently issued accounting pronouncements that may potentially impact our financial position and results of operations is disclosed in Note 2 to our consolidated financial statements. 104
To date, there have not been any material adjustments to our prior estimates of accrued research and development expenses. Recently Issued Accounting Pronouncements A description of recently issued accounting pronouncements that may potentially impact our financial position and results of operations is disclosed in Note 2 to our consolidated financial statements.
We are advancing a pipeline in which we have matched investigational therapies with diseases where they can make the greatest impact, based on well-defined mechanistic rationale, clear clinical outcomes and biomarkers, and rigorous preclinical data, agnostic of modality.
We are advancing a pipeline in which we have matched investigational therapies with diseases where we believe they can make the greatest impact, based on well-defined mechanistic rationale, clear clinical outcomes and biomarkers, and rigorous preclinical data, agnostic of modality.
As of December 31, 2024, we have funded our operations primarily through public offerings of our common stock, private sales of preferred stock, convertible notes, and through revenue from sales of RELYVRIO and ALBRIOZA in the U.S. and Canada, respectively between July 2022 and April 2024.
As of December 31, 2025, we have funded our operations primarily through public offerings of our common stock, private sales of preferred stock, convertible notes, and through revenue from sales of RELYVRIO and ALBRIOZA in the U.S. and Canada, respectively between July 2022 and April 2024.
Product candidates such as avexitide and AMX0035 in later stages of clinical development generally have higher development costs than those in earlier stages of clinical development, such as AMX0114, primarily due to the increased size and duration of later-stage clinical trials and related product manufacturing expenses.
Product candidates such as avexitide and AMX0035 in later stages of clinical development generally have higher development costs than those in earlier stages of clinical development, such as AMX0114 and AMX0318, primarily due to the increased size and duration of later-stage clinical trials and related product manufacturing expenses.
These employees work across multiple indications and, therefore, we do not track their costs by indication. Research and development activities are central to our business model.
These employees work across multiple indications and, therefore, we do not track their costs by indication. 95 Research and development activities are central to our business model.
In April 2024, we announced the Restructuring Plan designed to focus our resources on key clinical and preclinical programs. The restructuring included a reduction in force which reduced our workforce by approximately 70% and a decrease in external financial commitments outside our priority areas. As a result, our selling, general and administrative expenses decreased in 2024 as compared to 2023.
In April 2024, we announced the Restructuring Plan designed to focus our resources on key clinical and preclinical programs. The restructuring included a reduction in force which reduced our workforce by approximately 70% and a decrease in external financial commitments outside our priority areas. As a result, our selling, general and administrative expenses decreased in 2025 as compared to 2024.
We may never succeed in obtaining or maintaining, as applicable, regulatory approval for avexitide, AMX0035 or any other current or future product candidates. Selling, General and Administrative Expenses Selling, general and administrative expenses consist primarily of salaries and related costs for personnel in executive, finance, sales, marketing, as well as administrative functions.
We may never succeed in obtaining or maintaining, as applicable, regulatory approval for avexitide, AMX0035, AMX0114, AMX0318 or any other current or future product candidates. Selling, General and Administrative Expenses Selling, general and administrative expenses consist primarily of salaries and related costs for personnel in executive, finance, sales, marketing, as well as administrative functions.
Financing Activities During the year ended December 31, 2024, net cash provided by financing activities was $0.3 million. This amount consisted of $2.1 million of proceeds from exercises of stock options, offset by $1.8 million of withholding taxes paid on stock-based awards. During the year ended December 31, 2023, net cash provided by financing activities was $3.5 million.
During the year ended December 31, 2024, net cash provided by financing activities was $0.3 million. This amount consisted of $2.1 million of proceeds from exercises of stock options, offset by $1.8 million of withholding taxes paid on stock-based awards.
A change in the outcome of any of these variables with respect to the development of avexitide, AMX0035 or any other current or future product candidates could have a significant impact on the cost and timing associated with the development of our product candidates.
A change in the outcome of any of these variables with respect to the development of avexitide, AMX0035, AMX0114, AMX0318 or any other current or future product candidates could have a significant impact on the cost and timing associated with the development of our product candidates.
At this time, we cannot accurately estimate or know the nature, timing and costs of the efforts that will be necessary to complete the clinical development of avexitide, AMX0035 and any future product candidates.
At this time, we cannot accurately estimate or know the nature, timing and costs of the efforts that will be necessary to complete the clinical development of avexitide, AMX0035, AMX0114, AMX0318 and any future product candidates.
Despite a decline in research and development expenses in 2024 compared to 2023, we expect that our research and development expenses will increase in connection with our planned clinical development activities in the near term and in the future.
Despite a decline in research and development expenses in 2025 compared to 2024, we expect that our research and development expenses will increase in connection with our planned clinical development activities in the near term and in the future.
Acquired In-process Research and Development Expenses On July 9, 2024, we completed the acquisition of substantially all the assets and interests in the development, manufacture and commercialization of avexitide, an investigational, first-in-class GLP-1 receptor antagonist, from Eiger, or the Seller, or the Eiger Acquisition.
Acquired In-process Research and Development Expenses In July 2024, we completed the acquisition of substantially all the assets and interests in the development, manufacture and commercialization of avexitide, an investigational, first-in-class GLP-1 receptor antagonist, from Eiger, or the Eiger Acquisition.
We expect to incur significant expenses as we: • continue our research and development efforts of avexitide in PBH, or any other indications, and conduct clinical trials of avexitide; • continue our research and development efforts of AMX0035, including our ongoing Phase 2b/3 trial of AMX0035 in PSP and our ongoing Phase 2 trial of AMX0035 for the treatment of Wolfram syndrome; • continue to develop AMX0114, our antisense oligonucleotide, for the treatment of people living ALS; • pursue INDs of AMX0035 for additional indications; • conduct preclinical studies and clinical trials for AMX0035 for additional indications and for potential future product candidates; • seek to identify and develop, acquire or in-license additional product candidates; 100 • experience any delays or encounter any issues with any of the above, including but not limited to failed studies, complex results, safety issues, or other regulatory challenges; • develop the necessary processes, controls and manufacturing data to obtain marketing approval for current or future product candidates and to support manufacturing on a commercial scale; • seek regulatory approvals for any current or future product candidates that successfully complete clinical trials, if any; • incur expenses in preparation for commercialization for any approved product candidates related to product sales, marketing, manufacturing, and distribution; • hire and retain additional personnel, such as preclinical, clinical, quality assurance, regulatory affairs, manufacturing, distribution, legal, compliance, finance, general and administrative, commercial and scientific personnel; and • develop, maintain, expand and protect our intellectual property portfolio.
We expect to incur significant expenses as we: • continue our research and development efforts of avexitide in PBH, or any other indications, and conduct clinical trials of avexitide; • continue our research and development efforts of AMX0035, including our ongoing Phase 2 trial of AMX0035 for the treatment of Wolfram syndrome and winding down of the Phase 2b/3 trial of AMX0035 in PSP; • continue our research and development efforts of AMX0114, including our ongoing Phase 1 clinical trial of AMX0114 for the treatment of ALS; • pursue INDs of AMX0035 for additional indications; • conduct preclinical studies and clinical trials for AMX0035 for additional indications and for potential future product candidates; • continue our preclinical efforts of AMX0318, including advancing into IND-enabling studies in 2026; • seek to identify and develop, acquire or in-license additional product candidates; • experience any delays or encounter any issues with any of the above, including but not limited to failed studies, complex results, safety issues, or other regulatory challenges; • develop the necessary processes, controls and manufacturing data to obtain marketing approval for current or future product candidates and to support manufacturing on a commercial scale; • seek regulatory approvals for any current or future product candidates that successfully complete clinical trials, if any; • incur expenses in preparation for commercialization for any approved product candidates related to product sales, marketing, manufacturing, and distribution; • hire and retain additional personnel, such as preclinical, clinical, quality assurance, regulatory affairs, manufacturing, distribution, legal, compliance, finance, general and administrative, commercial and scientific personnel; and • develop, maintain, expand and protect our intellectual property portfolio.
In January 2025, we entered into an underwriting agreement with Leerink Partners LLC, as representative of the several underwriters named therein, relating to the issuance and sale of an aggregate of 19,714,285 shares of our common stock, which includes the exercise in full by the underwriters of their option to purchase an additional 2,571,428 shares, or the January 2025 Offering.
Liquidity and Capital Resources Sources of Liquidity In January 2025, we entered into an underwriting agreement with Leerink Partners LLC, as representative of the several underwriters named therein, relating to the issuance and sale of an aggregate of 19,714,285 shares of our common stock, which includes the exercise in full by the underwriter of its option to purchase an additional 2,571,428 shares, or the January 2025 Offering.
Our future funding requirements will depend on and could increase significantly as a result of many factors, including: • the scope, progress, results and costs of drug discovery, laboratory testing, preclinical and clinical development for avexitide, AMX0035 and any future product candidates; • the costs, timing and outcome of any future commercialization activities, including manufacturing, marketing, sales and distribution costs; • the costs, timing and outcome of regulatory review of avexitide, AMX0035 and any future product candidates; • our ability to establish and maintain collaborations, marketing, distribution and license agreements on favorable terms, if at all; • our ability to enroll clinical trials in a timely manner and to quickly resolve any delays or clinical holds that may be imposed on our development activities; • timing delays with respect to preclinical and clinical development of avexitide, AMX0035 and any future product candidates, including as result of any future outbreak of any highly infectious or contagious diseases; • costs associated with identifying and developing, acquiring or in-licensing additional product candidates or products; • the costs of any future expansion of our facilities to accommodate our potential growth in personnel, and the costs of such additional personnel; • the costs of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights and defending intellectual property-related claims; • the extent to which we acquire technologies or other assets; • the sales price and availability of adequate third-party coverage and reimbursement for any future product candidates, if and when approved; • the costs of current and potential legal proceedings that may not be covered by our insurance; and • the costs of operating as a public company. 101 Until such time, if ever, that we can generate product revenue sufficient to sustain profitability, we may finance our cash needs through equity offerings, debt financings, government or other third-party funding, marketing and distribution arrangements and other collaborations, strategic alliances and licensing arrangements.
Our future funding requirements will depend on and could increase significantly as a result of many factors, including: • the scope, progress, results and costs of drug discovery, laboratory testing, preclinical and clinical development for avexitide, AMX0035, AMX0114, AMX0318 and any future product candidates; • the costs, timing and outcome of any future commercialization activities, including manufacturing, marketing, sales and distribution costs; • the costs, timing and outcome of regulatory review of avexitide, AMX0035, AMX0114, AMX0318 and any future product candidates; • our ability to establish and maintain collaborations, marketing, distribution and license agreements on favorable terms, if at all; • our ability to enroll clinical trials in a timely manner and to quickly resolve any delays or clinical holds that may be imposed on our development activities; 100 • timing delays with respect to preclinical and clinical development of avexitide, AMX0035, AMX0114, AMX0318 and any future product candidates, including as result of any future outbreak of any highly infectious or contagious diseases; • costs associated with identifying and developing, acquiring or in-licensing additional product candidates or products; • the costs of any future expansion of our facilities to accommodate our potential growth in personnel, and the costs of such additional personnel; • the costs of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights and defending intellectual property-related claims; • the extent to which we acquire technologies or other assets; • the sales price and availability of adequate third-party coverage and reimbursement for any future product candidates, if and when approved; • the costs of current and potential legal proceedings that may not be covered by our insurance; and • the costs of operating as a public company.
These expenses include: • expenses incurred under agreements with CROs, contract manufacturing organizations, or CMOs, as well as investigative sites and consultants that conduct our clinical trials, preclinical studies and other scientific development services; • manufacturing scale-up expenses and the cost of acquiring and manufacturing drug product for our preclinical studies and clinical trials, including manufacturing registration and validation batches, as well as pre-commercial manufacturing activities; • expenses to acquire technologies to be used in research and development; • employee-related expenses, including salaries, payroll taxes, related benefits and stock-based compensation expense for employees engaged in research and development functions; and • costs related to compliance with quality and regulatory requirements. 95 Advance payments that we make for goods or services to be received in the future for use in research and development activities are recorded as prepaid expenses.
These expenses include: • expenses incurred under agreements with CROs, CMOs, as well as investigative sites and consultants that conduct our clinical trials, preclinical studies and other scientific development services; • manufacturing scale-up expenses and the cost of acquiring and manufacturing drug product for our preclinical studies and clinical trials, including manufacturing registration and validation batches, as well as pre-commercial manufacturing activities; • expenses to acquire technologies to be used in research and development; • employee-related expenses, including salaries, payroll taxes, related benefits and stock-based compensation expense for employees engaged in research and development functions; and • costs related to compliance with quality and regulatory requirements.
Research and Development Expenses Research and development expenses consist primarily of costs incurred in connection with the research and development of avexitide, AMX0035, AMX0114 and other potential future product candidates. We expense research and development costs as incurred.
Components of Our Results of Operations Operating Expenses Research and Development Expenses Research and development expenses consist primarily of costs incurred in connection with the research and development of avexitide, AMX0035, AMX0114, AMX0318 and other potential future product candidates. We expense research and development costs as incurred.
Cost of sales consisted of costs to procure, manufacture and distribute our marketed products, RELYVRIO and ALBRIOZA. As a result of the RELYVRIO®/ALBRIOZA™ Discontinuation, we recorded approximately $118.7 million of charges associated with the write-down of inventory and losses on firm purchase commitments for the year ended December 31, 2024.
As a result of the RELYVRIO®/ALBRIOZA™ Discontinuation, we recorded approximately $118.7 million of charges associated with the write-down of inventory and losses on firm purchase commitments for the year ended December 31, 2024.
The decrease was primarily due to a decrease of $39.5 million in payroll and personnel-related costs, $25.5 million in consulting and professional services, and $9.1 million in other expenses. The decrease in payroll and personnel-related costs was primarily related to a decrease in the number of employees as a result of the Restructuring Plan.
The decrease was primarily due to a decrease of $15.0 million in payroll and personnel-related costs, $15.7 million in consulting and professional services, and $20.7 million in other expenses. The decrease in payroll and personnel-related costs was primarily related to a decrease in the number of employees as a result of the Restructuring Plan.
This was offset by a $73.1 million increase in inventories, a $24.7 million increase in accounts receivable, a $4.8 million increase in prepaid expenses and other current assets and a $2.0 million decrease in operating lease liabilities. 102 Investing Activities During the year ended December 31, 2024, net cash provided by investing activities was $75.7 million resulting from $344.0 million of investments that matured during the period offset by $232.0 million in purchases of marketable securities and a $36.2 million cash outflow to acquire IPR&D assets related to the Eiger Acquisition.
During the year ended December 31, 2024, net cash provided by investing activities was $75.7 million resulting from $344.0 million of investments that matured during the period offset by $232.0 million in purchases of marketable securities and a $36.2 million cash outflow to acquire IPR&D assets related to the Eiger Acquisition.
The decrease of $24.1 million was primarily due to a $24.1 million decrease in spending on AMX0035 for the treatment of ALS following topline data from the PHOENIX trial in April 2024, an $8.1 million decrease in payroll and personnel-related costs due to a decrease in the number of employees following the completion of our Restructuring Plan, and a $5.2 million decrease in other costs due to an decrease in preclinical development activities.
The decrease of $13.7 million was primarily due to a $35.0 million decrease in spending on AMX0035 for the treatment of ALS following topline data from the PHOENIX trial and a $6.7 million decrease in payroll and personnel-related costs due to a decrease in the number of employees following the completion of our Restructuring Plan.
Under the restructuring, we reduced our workforce by approximately 70% and decreased external financial commitments outside of our priority areas. Restructuring expenses were approximately $22.9 million for the year ended December 31, 2024 which includes employee severance and termination benefits of approximately $21.9 million, contract termination costs, impairment of long-lived assets and other costs of $1.0 million.
Restructuring Expenses We did not recognize restructuring expenses for the year ended December 31, 2025. During the year ended December 31, 2024, restructuring expenses were approximately $22.9 million, which includes employee severance and termination benefits of approximately $21.9 million, contract termination costs, impairment of long-lived assets and other costs of $1.0 million.
Capital Resources Despite the decline in research and development and general administrative expenses in 2024 as compared to 2023, we expect our expenses to increase in connection with our ongoing activities, particularly as we advance the preclinical activities, manufacturing and clinical trials of avexitide, AMX0035 and any other current or future product candidates or acquire or in-license additional product candidates or products.
There can be no assurances that our current operating plan will be achieved or that additional funding, if required, will be available on terms acceptable to us, or at all. 99 Capital Resources and Uses Despite the decline in research and development and general administrative expenses in 2025 as compared to 2024, we expect our expenses to increase in connection with our ongoing activities, particularly as we advance the preclinical activities, manufacturing and clinical trials of avexitide, AMX0035, AMX0114 and any other current or future product candidates or acquire or in-license additional product candidates or products.
We are currently developing three investigational therapies for potential impact across several diseases: avexitide in PBH and congenital HI, AMX0035 in Wolfram syndrome and PSP, and AMX0114 in ALS. As of December 31, 2024, we had cash, cash equivalents and marketable securities of $176.5 million. In January 2025, we received net proceeds of $65.5 million from the January 2025 Offering.
We are currently developing four investigational therapies for potential impact across several diseases: avexitide in PBH, AMX0035 in Wolfram syndrome, AMX0114 in ALS, and AMX0318 in PBH and other rare diseases. As of December 31, 2025, we had cash, cash equivalents and marketable securities of $317.0 million.
During the year ended December 31, 2023, net cash provided by investing activities was $92.1 million resulting from $394.1 million of investments matured during the period offset by $300.8 million in purchases of marketable securities and $1.2 million in purchases of property and equipment.
Investing Activities During the year ended December 31, 2025, net cash provided by investing activities was $14.0 million resulting primarily from $246.0 million of investments that matured, offset by $231.8 million in purchases of marketable securities.
We have based this estimate on assumptions that may prove to be wrong, and we could exhaust our available capital resources sooner than we expect.
We believe our existing cash, cash equivalents and marketable securities as of December 31, 2025 will be sufficient to fund our operations into 2028. We have based this estimate on assumptions that may prove to be wrong, and we could exhaust our available capital resources sooner than we expect.
The decrease in consulting and professional services was primarily due to a decrease in commercial sales and marketing activity as a result of the RELYVRIO®/ALBRIOZA™ Discontinuation. The decrease in other expenses is primarily due to a decrease in charitable contributions. Restructuring Expenses In April 2024, we announced a restructuring to focus our financial resources on upcoming clinical milestones.
The decrease in consulting and professional services was primarily due to a decrease in commercial sales and marketing activity as a result of the RELYVRIO®/ALBRIOZA™ Discontinuation. The decrease in other expenses is primarily due to a decrease in charitable contributions, lower facilities and IT-related expenses, and a decrease in activity to wind down commercial operations.
The offering price per share was $3.50. The January 2025 Offering resulted in estimated proceeds of approximately $65.5 million, net of underwriting discounts and estimated offering expenses (see Note 18 Subsequent events). As of December 31, 2024, we had cash, cash equivalents and marketable securities of $176.5 million and an accumulated deficit of $606.7 million.
The public offering price per share was $10.00. The September 2025 Offering resulted in proceeds of approximately $190.7 million, net of underwriting discounts and offering expenses. As of December 31, 2025, we had cash, cash equivalents and marketable securities of $317.0 million and an accumulated deficit of $751.4 million.
We evaluate and adjust these costs as appropriate for changes in circumstances as additional information becomes available. Income Taxes We have historically not incurred significant income taxes. We continue to maintain a full valuation allowance against all of our deferred tax assets based on management’s evaluation of all available evidence, including our history of incurring significant losses from operations.
We continue to maintain a full valuation allowance against all of our deferred tax assets based on management’s evaluation of all available evidence, including our history of incurring significant losses from operations. As a result, we don’t expect to incur material income taxes for the foreseeable future.
Our inability to raise capital or secure other funding as and when needed could have a negative impact on our financial condition and ability to pursue our business strategies. There can be no assurances that our current operating plan will be achieved or that additional funding, if required, will be available on terms acceptable to us, or at all.
Our inability to raise capital or secure other funding as and when needed could have a negative impact on our financial condition and ability to pursue our business strategies.
As of December 31, 2024, the amounts committed under these agreements are not material. Critical Accounting Policies and Significant Judgments and Estimates Our consolidated financial statements are prepared in accordance with U.S. GAAP.
Critical Accounting Policies and Significant Judgments and Estimates Our consolidated financial statements are prepared in accordance with U.S. generally accepted accounting principles, or U.S. GAAP.
We have based this estimate on assumptions that may prove to be wrong, and we could exhaust our available capital resources sooner than we expect.
We believe our existing cash, cash equivalents and marketable securities as of December 31, 2025 will be sufficient to fund our operations into 2028. We have based this estimate on assumptions that may prove to be wrong, and we could exhaust our available capital resources sooner than we expect. See “Liquidity and Capital Resources” below.
Cash Flows Comparison of the Years Ended December 31, 2024 and 2023 The following table summarizes our sources and uses of cash for the years ended December 31, 2024 and 2023: Year Ended December 31, 2024 2023 $ Change % Change (in thousands) Net cash (used in) provided by operating activities $ (167,647 ) $ 11,919 $ (179,566 ) (1,507 )% Net cash provided by investing activities 75,654 92,053 (16,399 ) (18 )% Net cash provided by financing activities 348 3,543 (3,195 ) (90 )% Effect of exchange rate changes on cash, cash equivalents and restricted cash equivalents (438 ) 160 (598 ) (374 )% Net (decrease) increase in cash, cash equivalents and restricted cash equivalents $ (92,083 ) $ 107,675 $ (199,758 ) (186 )% Operating Activities During the year ended December 31, 2024, operating activities used $167.6 million of cash, primarily resulting from our net loss of $301.7 million, offset by non-cash items totaling $179.9 million including $118.7 million of inventory impairment and loss on firm purchase commitments, $33.0 million of non-cash stock-based compensation expense, $9.9 million in accretion of discounts on investments and $36.2 million of acquired IPR&D assets, which are classified as investing activities.
Net cash used by changes in our operating assets and liabilities primarily consisted of a $6.6 million decrease in accrued expenses, a $1.2 million decrease in operating lease liabilities, and a $2.0 million increase in other assets, offset by a $6.0 million decrease in prepaid expenses and other current assets and a $1.7 million decrease in operating right-of-use (ROU) assets. 101 During the year ended December 31, 2024, operating activities used $167.6 million of cash, primarily resulting from our net loss of $301.7 million, offset by non-cash items totaling $179.9 million including $118.7 million of inventory impairment and loss on firm purchase commitments, $33.0 million of non-cash stock-based compensation expense, $9.9 million in accretion of discounts on investments and $36.2 million of acquired IPR&D assets, which are classified as investing activities.
Product revenue, net was related to units of RELYVRIO and ALBRIOZA sold in the U.S. and Canada, respectively, prior to the RELYVRIO®/ALBRIOZA™ Discontinuation. Cost of sales Cost of sales were $124.6 million for the year ended December 31, 2024, compared to $25.4 million for the year ended December 31, 2023.
As a result of the RELYVRIO®/ALBRIOZA™ Discontinuation, we did not generate revenue from product sales for the year ended December 31, 2025. For the year ended December 31, 2024, product revenue, net was primarily related to units of RELYVRIO and ALBRIOZA previously sold in the U.S. and Canada during the first quarter of 2024.
During the year ended December 31, 2024, we recorded a charge of approximately $36.2 million associated with the acquired in-process research and development assets of avexitide with no alternative future use. 98 Research and Development Expenses The following table summarizes our research and development expenses for the years ended December 31, 2024 and 2023: Year Ended December 31, 2024 2023 $ Change % Change (in thousands) Direct research and development expenses by program: AMX0035 - ALS $ 36,727 $ 60,843 $ (24,116 ) (40 )% AMX0035 - PSP 16,917 6,404 10,513 164 % Avexitide 2,766 — 2,766 *NM Other programs 8,698 13,870 (5,172 ) (37 )% Total direct research and development expenses by program 65,108 81,117 (16,009 ) (20 )% Personnel-related research and development 38,976 47,070 (8,094 ) (17 )% $ 104,084 $ 128,187 $ (24,103 ) (19 )% * NM - not meaningful Research and development expenses were $104.1 million for the year ended December 31, 2024, compared to $128.2 million for the year ended December 31, 2023.
Research and Development Expenses The following table summarizes our research and development expenses for the years ended December 31, 2025 and 2024: Year Ended December 31, 2025 2024 $ Change % Change (in thousands) Direct research and development expenses by program: Avexitide $ 24,100 $ 2,766 $ 21,334 771 % AMX0035 - PSP 17,260 16,917 343 2 % AMX0035 - ALS 1,756 36,727 (34,971 ) (95 )% Other programs 15,004 8,698 6,306 72 % Total direct research and development expenses by program 58,120 65,108 (6,988 ) (11 )% Personnel-related research and development 32,284 38,976 (6,692 ) (17 )% $ 90,404 $ 104,084 $ (13,680 ) (13 )% Research and development expenses were $90.4 million for the year ended December 31, 2025, compared to $104.1 million for the year ended December 31, 2024.
The increase in spending on AMX0035 for the treatment of PSP was primarily related to costs to support the continuation of the ORION Phase 2b/3 global clinical trial. Selling, General and Administrative Expenses Selling, general and administrative expenses were $114.3 million for the year ended December 31, 2024 compared to $188.4 million for the year ended December 31, 2023.
The decrease in research and development expenses was offset by a $21.3 million increase in expenses related to the pivotal Phase 3 LUCIDITY clinical trial in PBH and other costs related to avexitide, and a $6.3 million increase in other research and development activities. 98 Selling, General and Administrative Expenses Selling, general and administrative expenses were $62.9 million for the year ended December 31, 2025 compared to $114.3 million for the year ended December 31, 2024.
This amount consisted of $7.0 million of proceeds from exercises of stock options, offset by $3.3 million of withholding taxes paid on stock-based awards and $0.1 million in payments of deferred offering costs. Contractual Obligations and Commitments We enter into agreements in the normal course of business with contract manufacturing organizations for raw material purchases and manufacturing services.
Contractual Obligations and Commitments We enter into agreements in the normal course of business with contract manufacturing organizations for raw material purchases and manufacturing services. As of December 31, 2025, there are no amounts committed under these agreements.
However, we expect that general and administrative expenses will increase in future periods as we advance our clinical pipeline. Restructuring Expenses Restructuring expenses consists primarily of employee severance and termination benefits, contract termination costs, impairment of long-lived assets and other costs. Such costs are based on estimates of fair value in the period liabilities are incurred.
However, we expect that general and administrative expenses will increase in future periods as we advance our clinical pipeline. Income Taxes We have historically not incurred significant income taxes.
Removed
We believe our existing cash, cash equivalents and marketable securities as of December 31, 2024, along with the proceeds from the January 2025 Offering, will be sufficient to meet our anticipated operating and capital expenditure requirements through 2026.
Added
Advance payments that we make for goods or services to be received in the future for use in research and development activities are recorded as prepaid expenses.
Removed
See “Liquidity and Capital Resources” below. 94 Components of Our Results of Operations Product Revenue, Net Product revenue, net recognized during the years ended December 31, 2024 and 2023 relates to units of ALBRIOZA and RELYVRIO sold in Canada and the U.S., respectively.
Added
As a result of the RELYVRIO®/ALBRIOZA™ Discontinuation, we did not generate cost of sales for the year ended December 31, 2025. For the year ended December 31, 2024, cost of sales consisted of costs to procure, manufacture and distribute our marketed products, RELYVRIO and ALBRIOZA.
Removed
In April 2024, we announced we had started a process with the FDA and Health Canada to voluntarily discontinue the marketing authorizations for RELYVRIO®/ALBRIOZA™ (sodium phenylbutyrate and taurursodiol [also known as ursodoxicoltaurine]; also known as AMX0035) for the treatment of ALS and remove the product from the market in the U.S. and Canada, or the “RELYVRIO®/ALBRIOZA™ Discontinuation.
Added
During the year ended December 31, 2024, we recorded a charge of approximately $36.2 million associated with the acquired in-process research and development assets of avexitide with no alternative future use.
Removed
This decision was informed by topline results from the global Phase 3 PHOENIX trial, which failed to meet its prespecified primary and secondary endpoints, engagement with regulatory authorities, and discussions with the ALS community. As a result, we do not expect to generate revenue from the sale of RELYVRIO®/ALBRIOZA™ in future periods.
Added
We substantially completed the Restructuring Plan in the second quarter of 2024.
Removed
As of April 4, 2024, RELYVRIO/ALBRIOZA was no longer available for new patients. Patients who were currently on therapy in the U.S. and Canada who, in consultation with their physician, wished to stay on treatment had the option to be transitioned to a free drug program.
Added
The public offering price per share was $3.50. The January 2025 Offering resulted in proceeds of approximately $65.5 million, net of underwriting discounts and offering expenses.
Removed
Patients and their physicians were informed that final shipments of free drug were made to allow treatment through early 2025. The NDA is now on the Discontinued Drug Product List of the Orange Book and we have filed a formal request to withdraw the NDA.
Added
In September 2025, we entered into an underwriting agreement with Leerink Partners LLC and Guggenheim Securities LLC, as representatives of the several underwriters named therein, relating to the issuance and sale of an aggregate of 20,150,000 shares of our common stock, which includes the exercise in full by the underwriters of their option to purchase an additional 2,625,000 shares, or the September 2025 Offering.
Removed
We have completed the collection of data on survival and we will continue to share any learnings from PHOENIX to help inform future ALS research. We wound down the Open Label Extension as planned.
Added
Until such time, if ever, that we can generate product revenue sufficient to sustain profitability, we may finance our cash needs through equity offerings, debt financings, government or other third-party funding, marketing and distribution arrangements and other collaborations, strategic alliances and licensing arrangements.
Removed
Operating Expenses Cost of Sales Cost of sales consists primarily of costs associated with the manufacturing of RELYVRIO, ALBRIOZA and certain period costs and losses on purchase commitments with contract manufacturing organizations.
Added
Cash Flows Comparison of the Years Ended December 31, 2025 and 2024 The following table summarizes our sources and uses of cash for the years ended December 31, 2025 and 2024: Year Ended December 31, 2025 2024 $ Change % Change (in thousands) Net cash used in operating activities $ (123,343 ) $ (167,647 ) $ 44,304 (26 )% Net cash provided by investing activities 14,039 75,654 (61,615 ) (81 )% Net cash provided by financing activities 257,029 348 256,681 73,759 % Effect of exchange rate changes on cash, cash equivalents and restricted cash equivalents 1,074 (438 ) 1,512 (345 )% Net increase (decrease) in cash, cash equivalents and restricted cash equivalents $ 148,799 $ (92,083 ) $ 240,882 (262 )% Operating Activities During the year ended December 31, 2025, operating activities used $123.3 million of cash, primarily resulting from our net loss of $144.7 million, $5.5 million in accretion of discounts on investments, and $1.1 million of net cash used by changes in our operating assets and liabilities, offset by $27.6 million of non-cash stock-based compensation expense.
Removed
Following our announcement of a process to discontinue the marketing authorizations for RELYVRIO®/ALBRIOZA™ and remove the product from the market in the U.S. and Canada, we did not report product cost of sales following the discontinuation of these products.
Added
Financing Activities During the year ended December 31, 2025, net cash provided by financing activities was $257.0 million. This amount consisted primarily of $65.6 million in proceeds from the January 2025 Offering, net of offering costs paid, and $190.7 million in proceeds from the September 2025 Offering, net of offering costs paid.
Removed
Acquired In-process Research and Development Expenses Acquired in-process research and development, or IPR&D, expenses relate to upfront or other payments pursuant to our business development transactions, including the Eiger Acquisition (as defined below).
Removed
The decrease in research and development expenses was offset by a $10.5 million increase in spending on AMX0035 for the treatment of PSP, and a $2.8 million increase in expenses for the development of avexitide following the Eiger Acquisition.
Removed
We completed the Restructuring Plan in 2024. 99 Liquidity and Capital Resources Sources of Liquidity In the second half of 2022, we began generating revenue from the sale of our approved drug product RELYVRIO, known as ALBRIOZA in Canada. In April 2024, we announced the RELYVRIO®/ALBRIOZA™ Discontinuation.
Removed
We also announced the Restructuring Plan, which was designed to focus our resources on key clinical and preclinical programs and included a reduction in force which reduced our workforce by approximately 70% and decreased external financial commitments outside of our priority areas. We completed the Restructuring Plan in the second half of 2024.
Removed
We believe our existing cash, cash equivalents and marketable securities as of December 31, 2024, along with the proceeds from the January 2025 Offering, will be sufficient to meet our anticipated operating and capital expenditure requirements through 2026.
Removed
During the year ended December 31, 2023, operating activities provided $11.9 million of cash, primarily resulting from our net income of $49.3 million, non-cash stock-based compensation expense of $37.2 million and $1.1 million of depreciation expense, offset by an increase of $65.7 million in net cash used in our operating assets and liabilities and net amortization of premiums and discounts on investments of $9.9 million.
Removed
Net cash used in our operating assets and liabilities in 2023 primarily consisted of a $21.6 million increase in accrued expenses, a $15.9 million increase in accounts payable and a $1.8 million decrease in operating lease right-of-use assets.
Removed
Revenue Recognition Prior to the RELYVRIO®/ALBRIOZA™ Discontinuation, our accounting policy for revenue recognition had a substantial impact on reported results and relied on certain estimates. Specifically, revenue was reduced by variable consideration related to certain gross-to-net, or GTN.
Removed
These GTN adjustments involve significant estimates and judgment, considering historical experience, payer channel mix (e.g., Medicare or Medicaid), current contract prices under applicable programs, unbilled claims and processing time lags and inventory levels in the distribution channel. Estimates were assessed each period and adjusted as required to revise information or actual experience.
Removed
To date, actual GTN activity has not differed materially from our estimates. Because of the time elapsed since the RELYVRIO®/ALBRIOZA™ Discontinuation the remaining estimates and judgments related to revenue recognition are not considered significant as of December 31, 2024.

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