What changed in this filing

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Item 1. Business

2026-03-03 compared with 2025-03-04 · 162 added, 132 removed, 615 unchanged (32% of the section changed)

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(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.

We have preclinical and clinical development programs underway in endocrine conditions and neurodegenerative diseases.

We are advancing a pipeline in which we have matched investigational therapies with diseases for which we believe these therapies can make the greatest impact, based on well-defined mechanistic rationales, clear clinical outcomes and biomarkers, and rigorous preclinical data, agnostic of modality.

Our current pipeline is represented in the table below.

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.

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.

In PBH, an indication with no currently approved treatment options impacting approximately 160,000 people in the U.S., excessive GLP-1 can lead to the hypersecretion of insulin and subsequent persistent, recurrent, and debilitating hypoglycemic events, including autonomic and neuroglycopenic symptoms if left unaddressed.

Avexitide is designed to bind to the GLP-1 receptor on pancreatic islet beta cells, inhibiting the effect of GLP-1 to mitigate hypoglycemia by decreasing insulin secretion and stabilizing blood glucose levels.

In February 2025, we started recruiting for the pivotal Phase 3 LUCIDITY clinical trial for avexitide in PBH.

LUCIDITY (NCT06747468) is a multicenter, randomized, double-blind, placebo-controlled, 16-week clinical trial evaluating the efficacy and safety of avexitide in participants with PBH following Roux-en-Y gastric bypass, or RYGB surgery.

The Phase 3 trial is being conducted at approximately 20 sites in the U.S.

Approximately 75 participants will be randomized 3:2 to receive either 90 mg of avexitide subcutaneously once daily or placebo.

Dosing is expected to begin in March or April of 2025.

Participants who complete the 16-week double-blind period of the ongoing study will be eligible to enter an open-label extension, or OLE period with a duration of 32 weeks.

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.

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.

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.

Post-bariatric hypoglycemia (PBH) is a condition that is estimated to affect approximately 8% of people in the U.S.

who have undergone the two most common types of bariatric surgery, sleeve gastrectomy and Roux-en-Y gastric bypass (approximately 160,000 people in the U.S.).

PBH is thought to be caused by an excessive glucagon-like peptide-1 (GLP-1) response leading to hypoglycemia and impaired quality of life.

PBH can cause debilitating hypoglycemic events associated with inadequate supply of glucose to the brain, known as neuroglycopenia.

Clinical manifestations can include impaired cognition, loss of consciousness, and seizures.

PBH is also associated with a high degree of disability that can result in major disruptions to independent living.

There are no approved therapies for PBH.

Avexitide is designed to bind to the GLP-1 receptor on pancreatic islet beta cells and inhibit the effect of GLP-1 to mitigate hypoglycemia by decreasing insulin secretion and stabilizing blood glucose levels.

LUCIDITY (NCT06747468) is an approximately 75-participant, multicenter, randomized, double-blind, placebo-controlled Phase 3 clinical trial evaluating the efficacy and safety of avexitide in participants with PBH following RYGB surgery.

The Phase 3 trial is being conducted at 21 sites in the U.S.

Participants will be randomized 3:2 to receive either 90 mg of avexitide subcutaneously once daily or placebo.

The trial includes an up to six-week screening period, including a three-week run-in period, and a 16-week double-blind treatment period.

Participants who complete the double-blind period will be eligible to enter an open-label extension, or OLE, period with a duration of 32 weeks.

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.

Completion of recruitment is expected in 2025, with topline data anticipated in the first half of 2026 and, if approved, commercial launch anticipated in 2027.

Recruitment of LUCIDITY is complete.

We continue to expect to randomize and dose the last eligible patients in Q1 2026 with topline data expected in Q3 2026, and if approved, a commercial launch in 2027.

LUCIDITY was informed by data from five clinical trials of avexitide in people with PBH showing consistent, dose-dependent effects across studies.

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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.

• 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.

Participants in the Phase 2b trial receiving 90 mg once daily of avexitide, the dose Amylyx is evaluating in LUCIDITY, saw a statistically significant 53% reduction in Level 2 hypoglycemic events (p=0.004) and a statistically significant 66% reduction in Level 3 hypoglycemic events (p=0.0003).

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In addition, avexitide demonstrated a clear GLP-1 antagonist pharmacodynamic effect, including lowering insulin and raising the glucose nadir, in healthy volunteers.

In July 2025, we presented new exploratory analyses from the Phase 2 PREVENT and Phase 2b clinical trials of avexitide for the treatment of PBH at the Endocrine Society’s annual meeting.

In the Phase 2b trial, avexitide 90 mg once daily led to a 64% least-squares mean reduction (p=0.0031) versus baseline in the composite rate of Level 2 and Level 3 hypoglycemic events in PBH, with more than half of the participants experiencing no events during the treatment period.

The 45 mg twice daily, 30 mg twice daily, and 60 mg once daily dose regimens all likewise demonstrated consistent reductions in composite rate of Level 2 and Level 3 hypoglycemic events.

New pharmacokinetic and pharmacodynamic data were also presented, demonstrating continuous pharmacologic activity of the 90 mg once daily dose regimen for a 24-hour period.

In Congenital HI, we are actively engaging in discussions with the broader Congenital HI community to develop a path forward.

In December 2024, we announced a collaboration with Gubra A/S for the development of a potential novel long-acting GLP-1 receptor antagonist.

As part of this collaboration, we anticipate identifying a lead development candidate to enter Investigational New Drug, or IND-enabling studies.

In addition to avexitide, we are advancing AMX0035, an oral, fixed-dose combination of sodium phenylbutyrate and taurursodiol in Wolfram syndrome and PSP, and AMX0114 in amyotrophic lateral sclerosis, or ALS.

In addition to avexitide, we are advancing AMX0035, an oral, fixed-dose combination of sodium phenylbutyrate and taurursodiol in Wolfram syndrome, AMX0114 in ALS and AMX0318 in PBH and other rare diseases.

AMX0035 is designed to mitigate neurodegeneration by targeting endoplasmic reticulum, or ER, stress and mitochondrial dysfunction, two cellular processes central to neuronal cell death and neurodegeneration.

We are investigating AMX0035 in neurodegenerative diseases and endocrine conditions where ER stress and mitochondrial dysfunction are implicated, including Wolfram syndrome and PSP.

We are investigating

AMX0035 in Wolfram syndrome, a neurodegenerative disease where ER stress and mitochondrial dysfunction are implicated.

Wolfram syndrome is a rare, monogenic neurodegenerative disease that progressively impacts multiple organs and systems.

Wolfram syndrome is characterized by childhood-onset diabetes mellitus, optic nerve atrophy, and neurodegeneration.

Common manifestations of Wolfram syndrome include diabetes mellitus and diabetes insipidus, gradual vision loss leading to blindness, hearing loss, neurogenic bladder, difficulties with balance and coordination, and difficulty

breathing that can lead to respiratory failure.

There are currently no approved therapies for the approximately 3,000 people in the U.S., and more around the world, living with Wolfram syndrome.

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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.

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.

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.

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.

Consistent with the HELIOS trial’s previously presented primary efficacy outcome of improvement in pancreatic function (as described below), treatment with AMX0035 through Week 48 demonstrated continued and sustained improvement in pancreatic beta cell function.

Treatment with AMX0035 from Week 24 to Week 48 also showed sustained improvements or stabilization in glycemic control, as measured by hemoglobin A1c, or HbA1c, and time in target glucose range assessed by continuous glucose monitoring, as well as visual acuity.

All participants with available measurements met the responder criteria, defined as either improvement or no change, on both the Patient Global Impression of Change and Clinician Global Impression of Change at Weeks 24 and 48, indicating stability or improvement in their Wolfram syndrome-related symptoms.

Results from qualitative on-study interviews further supported the potential positive impact of AMX0035 on symptom burden.

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.

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In addition, longer-term data for all participants who completed Week 36 (n=10) and Week 48 (n=6) assessments showed sustained improvement over time.

The safety profile of AMX0035 in HELIOS was consistent with prior safety data from the study of AMX0035 in ALS.

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 plan to share Week 48 data from the ongoing HELIOS trial of AMX0035 in Wolfram syndrome in 2025.

Data from participants at Week 48 and regulatory interactions will inform the design of a Phase 3 trial of AMX0035 in Wolfram syndrome.

PSP is a sporadic, rare, fatal neurodegenerative disease that can affect movement, gait, balance, cognition, eye movements, swallowing, and speech.

People living with PSP have a life expectancy of six to eight years after symptom onset.

PSP affects approximately seven in 100,000 people worldwide, and there are currently no disease-modifying therapies approved for the treatment of PSP.

Similar to other neurodegenerative diseases, the pathophysiologic changes underlying PSP are likely multifactorial, including genetic mutations, ER stress, mitochondrial dysfunction, and neuroinflammation.

PSP is considered a tauopathy based on the strong genetic link between tau variants and disease development and the presence of abnormal tau protein deposits in the brain.

Biomarker data from a Phase 2 trial of AMX0035 in Alzheimer’s disease demonstrated a significant reduction in tau.

In December 2023, we initiated the Phase 2b/3 ORION (NCT06122662) clinical trial, a global, randomized, double-blind, placebo-controlled trial of AMX0035 for the treatment of PSP.

ORION is designed to assess the efficacy and safety of AMX0035 compared to placebo.

The primary objective of the ORION trial is to assess the impact of AMX0035 compared to placebo on disease progression rate as measured by the Progressive Supranuclear Palsy Rating Scale, or PSPRS, an established and validated endpoint in PSP clinical trials.

Safety and tolerability will also be evaluated.

Data from an unblinded interim analysis of the Phase 2b portion of the Phase 2b/3 ORION trial of AMX0035 in PSP is anticipated in the third quarter of 2025, which will be used to inform a go/no-go decision on the Phase 3 portion of the trial.

We continue to work with the FDA on a Phase 3 trial in Wolfram syndrome.

In addition, Amylyx is committed to supporting medically and scientifically sound research, including externally-sponsored research conducted with an institution or organization.

Breakthrough T1D has provided funding to University of Washington and Amsterdam University Medical Center for a trial investigating AMX0035 as adjunctive therapy for treatment of insulin resistance in type 1 diabetes (T1D).

Amylyx will provide clinical trial supply of AMX0035.

AMX0114 is an investigational antisense oligonucleotide, or ASO, targeting calpain-2, or CAPN2 .

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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.

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.

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.

In February 2025, we started recruiting for the Phase 1 LUMINA clinical trial (NCT06665165), a multicenter, randomized, placebo-controlled, multiple ascending dose trial designed to evaluate the safety and biological activity of AMX0114.

LUMINA will also assess ALS biomarkers, including change from baseline in NfL levels.

Dosing is expected to begin in March or April of 2025.

We are also working to open U.S.

sites for screening, enrollment, and dosing.

In April 2025, the first participant was dosed in the Phase 1 LUMINA clinical trial (NCT06665165), a multicenter, randomized, double-blind, placebo-controlled, multiple ascending dose trial designed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of AMX0114 in people living with ALS.

LUMINA is also assessing both novel and broadly researched ALS biomarkers, including change from baseline in NfL levels.

Approximately 48 participants will be randomized 3:1 to receive AMX0114 or placebo by intrathecal administration once every four weeks, for up to four doses.

Early cohort data from LUMINA are expected in 2025.

In December 2025, we presented initial safety and tolerability data from Cohort 1 (n=12) of LUMINA demonstrating AMX0114 was generally well-tolerated, with no treatment-related serious AEs.

Cohort 1 biomarker data from LUMINA is expected to be presented at a medical meeting in the first half of 2026.

In September 2025, Cohort 1 was fully enrolled and in December 2025, we began enrolling Cohort 2 (n=12).

AMX0318 is a novel GLP-1 receptor antagonist for long-acting administration selected as a development candidate for PBH and other rare diseases in January 2026.

AMX0318 was selected as a development candidate after demonstrating robust preclinical and chemical properties, including a favorable pharmacokinetic profile that may support long-acting administration, a robust chemical stability profile, strong in vitro potency, evidence of in vivo efficacy and tolerability, and high solubility.

AMX0318 was identified through a research collaboration with Gubra A/S, a company specializing in peptide-based drug discovery and preclinical contract research services.

IND-enabling studies for AMX0318 are underway with an IND targeted for 2027.

The biotechnology and pharmaceutical industries are characterized by rapid technological advancement, significant competition and an emphasis on proprietary products.

We face potential competition from many different sources, including major and specialty pharmaceutical and biotechnology companies, academic research institutions, governmental agencies, compounding pharmacies and public and private research institutions.

Any product candidates that we successfully develop and commercialize may compete with current therapies and new therapies that may become available in the future.

Any product candidates that we successfully develop and commercialize may compete with current therapies and new therapies that may become available in the future that are approved to treat the same diseases for which we may obtain approval for our product candidates.

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.

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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.

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 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.

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.

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Intellectual Property

Our commercial success depends in part on our ability to obtain intellectual property that protects avexitide and its uses, AMX0035 and its uses, AMX0114 and its uses, and any future product candidates.

We seek to protect and enhance proprietary technology, inventions and improvements that are commercially important to the development of our business by seeking, maintaining and defending U.S.

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As of December 31, 2025, our patent estate included 23 issued U.S.

patents, 25 pending U.S.

patent applications, 211 granted foreign patents, and 109 pending foreign patent applications.

We acquired a patent portfolio directed to avexitide from Eiger Pharmaceuticals, Inc., or Eiger, in June 2024.

patents, 257 granted foreign patents, over 15 pending U.S.

patent applications, and over 115 pending foreign patent applications.

We acquired a patent portfolio directed to avexitide from Eiger Pharmaceuticals, Inc., or Eiger, in July of 2024.

The portfolio includes one in-licensed patent family from University of Pennsylvania/Children’s Hospital of Philadelphia, two in-licensed patent families from Stanford University, one co-owned with and in-licensed patent family from Stanford University, one patent family co-owned by us and Stanford University, and two patent families that are solely owned by us.

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One family relates to the treatment of hyperinsulinemic hypoglycemia with exendin(9-39).

There are currently no issued patents in this family.

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.

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.

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).

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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.

We have patent applications pending in this family in the U.S., EU, and other jurisdictions.

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.

Our patent portfolio around AMX0035 includes ten patent families.

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.

Our patent portfolio around AMX0035 includes fifteen patent families.

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.

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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

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.

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.

The issued patents and others that issue from our earliest in time patent family around AMX0035 may first begin to expire as early as December 2033, 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 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.

Our patent portfolio around AMX0114 includes 1 patent family.

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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.

While we have confidence in our agreements

and security measures, either may be breached, and we may not have adequate remedies.

In addition, our trade secrets may otherwise become known or independently discovered by competitors.

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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.

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.

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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.

As such, EP3016654 as maintained has no relevance for Wolfram Syndrome.

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.

A European divisional application is not pending in this family and can no longer be filed.

Government Regulation

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Progress reports detailing the results of the clinical trials must be submitted at least annually to the FDA and more frequently if suspected AEs occur.

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 sponsor must submit an IND safety report within 15 calendar days after the sponsor determines that the information qualifies for reporting.

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In most cases, the submission of an NDA is subject to a substantial application user fee.

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

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.

Under the Prescription Drug User Fee Act, or PDUFA, guidelines that are currently in effect, the FDA has a goal of ten months from the date of “filing” of a standard NDA, for a new molecular entity to review and act on the submission, and six months from the filing date of a new molecular entity NDA with priority review.

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.

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.

The FDA reviews an NDA to determine, among other things, whether the drug is safe and effective for its intended use(s), with the latter determination being made on the basis of substantial evidence.

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Even with submission of this additional information, the FDA ultimately may decide that the application does not satisfy the regulatory criteria for approval.

If and when those conditions have been met to the FDA’s satisfaction, the FDA will typically issue an

approval letter.

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.

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If a product with orphan status receives the first FDA approval for the disease or condition for which it has such designation or for a select indication or use within the rare disease or condition for which it was designated, the product is entitled to orphan product exclusivity.

Orphan product exclusivity means that the FDA may not approve any other applications to market the same product for the same indication for seven years, except in certain limited circumstances.

Orphan product exclusivity means that the FDA may not approve any other applications to market the same product for the same approved use or indication for seven years, except in certain limited circumstances.

If a drug designated as an orphan drug ultimately receives marketing approval for an indication broader than what it was designated for, it may not be entitled to exclusivity.

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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.

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 provides increased opportunities for sponsor interactions with the FDA during preclinical and clinical development, in addition to the potential for rolling review once a marketing application is filed, meaning that the agency may review portions of the marketing application before the sponsor submits the complete application, as well as priority review, discussed below.

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 benefits of Breakthrough Therapy Designation include the same benefits as Fast Track Designation, plus intensive guidance from the FDA to ensure an efficient drug development program.

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In October 2014, however, the FDA reversed that position when it issued final guidance stating that an application for a fixed-dose combination product will be eligible for 5-year NCE exclusivity if it contains a drug substance with a single, new active moiety, even if the fixed-combination also contains a drug substance with a previously approved active moiety.

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.

an existing drug.

This three-year exclusivity period covers only the conditions of use associated with the new clinical investigations and does not prohibit the FDA from approving follow-on applications that do not reference the protected clinical data.

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Pediatric exclusivity is another type of regulatory market exclusivity in the U.S.

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.

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.

This six-month exclusivity may be granted based on the voluntary completion of a pediatric trial in accordance with an FDA-issued “Written Request” for such a trial, provided that at the time pediatric exclusivity is granted there is not less than nine months of term remaining.

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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 stabilization period for building and validating interoperable electronic tracing systems has ended and trading partners who have not achieved compliance with these requirements must secure an exemption from the FDA.

Changes to the manufacturing process are strictly regulated and often require prior FDA approval before being implemented.

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From time to time, legislation is drafted, introduced, passed in Congress and signed into law that could significantly change the statutory provisions governing the approval, manufacturing, and marketing of products regulated by the FDA.

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.

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.

Healthcare Laws

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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.

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.

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;

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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.

For example, Washington’s My Health My Data Act, which entered into force on March 31, 2024, expands the definition of consumer health data, affords consumers with privacy rights and creates a private right of action, which could increase the risk of, and expenses related to, litigation.

While the CCPA contains an exception for certain activities involving PHI under HIPAA, we cannot yet determine the impact the CCPA or other such future laws, regulations and standards may have on our business, as these laws either do not yet apply to us or are not yet in effect.

Certain state laws may be more

stringent or broader in scope than others, or offer greater individual rights with respect to personal information than federal, international or other state laws with potentially conflicting requirements, which may complicate our compliance efforts.

While the CCPA and other state privacy laws contain exceptions for certain activities involving PHI under HIPAA, we cannot yet determine the impact the CCPA or other state privacy laws, regulations and standards may have on our business.

Certain state laws may be more stringent or broader in scope than others, or offer greater individual rights with respect to personal information than federal, international or other state laws with potentially conflicting requirements, which may complicate our compliance efforts.

Other states have passed privacy legislation that may be more restrictive and not preempted by HIPAA, such as those which apply specifically to consumer health data.

A smaller number of states have focused on more narrow aspects of privacy, including by passing legislation regulating the use and protection of biometric information.

Any failure or perceived failure to comply with any of these laws could negatively impact our business, including through enforcement actions, litigation and reputational harm leading to loss of existing and future business.

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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;

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.

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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.

In addition to provider payment cuts under Medicare, the American Rescue Plan Act of 2021 also eliminated the statutory Medicaid drug rebate cap, previously set at 100% of a drug’s average manufacturer price, for single source innovator multiple source drugs, beginning January 1, 2024.

In addition, the One Big Beautiful Bill Act of 2025, or the OBBBA, imposed significant reductions in Medicaid funding, additional work requirements for Medicaid recipients, and more frequent reenrollment requirements, which are expected to place substantial pressure on state Medicaid budgets, reduce enrollment, and limit covered services, which could decrease utilization of, and reimbursement for, our products, if approved.

These laws and regulations may result in additional reductions in Medicare and other healthcare funding available for healthcare providers and may otherwise affect the prices we may obtain for any of our product candidates for which we may obtain regulatory approval or the frequency with which any such product candidate is prescribed or used.

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;

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.

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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.

Further, under the IRA, orphan drugs are exempted from the Medicare drug price negotiation program, but only if they have one orphan designation and for which the only approved indication is for that disease or condition.

If a product receives multiple orphan designations or has multiple approved indications, it may not qualify for the orphan drug exemption.

Further, under the IRA, orphan

drugs are exempted from the Medicare drug price negotiation program, but only if their only approved indication(s) is for a rare disease or condition.

The implementation of the IRA is currently subject to ongoing litigation that challenges the constitutionality of the IRA’s Medicare drug price negotiation program.

The effects of the IRA on our business and the healthcare industry in general is not yet known.

The costs of prescription pharmaceuticals have also been the subject of considerable discussion in the United States.

To date, there have been several recent U.S.

congressional inquiries, as well as proposed and enacted federal and state legislation designed to, among other things, bring more transparency to drug pricing, review the relationship between pricing and manufacturer patient programs, reduce the costs of drugs under Medicare and reform government program reimbursement methodologies for drug products.

The Trump Administration has issued executive orders and supported proposed regulatory initiatives in 2025 that could have a significant impact on the prices that we, or any collaborators, may receive for any approved products.

On May 12, 2025, President Trump signed an executive order directing the Secretary of HHS to set and communicate most-favored-nation, or MFN, price targets to manufacturers and propose a rulemaking plan to impose MFN pricing if “significant progress” is not made, and also directing the federal government to support regulatory paths to allow direct-to-patient sales for companies that meet these targets.

The executive order further states that the Administration will take additional action (for example, examining whether marketing approvals should be modified or rescinded or considering individual drug importation waiver authorities) should manufacturers fail to offer American consumers the MFN lowest price.

In July 2025, President Trump sent letters to certain pharmaceutical companies demanding that these companies extend MFN pricing to Medicaid and newly launched drugs as well as move to direct-to-consumer models priced at MFN pricing, and soliciting binding commitments by September 29, 2025.

Since this time, multiple drug manufacturers have announced plans to, for certain of their drugs, lower priced to reflect similar pricing around the world, and to sell these reduced-price drugs on a direct-to-consumer purchasing platform developed by the federal government;

however, it is not known what results will occur to the extent the recipients of these letters do not reduce their U.S.

On December 19, 2025, CMS released two proposed rules that would incorporate MFN pricing principles into federal reimbursement for prescription drugs.

The first proposal, the Global Benchmark for Efficient Drug Pricing Model, or the GLOBE, for Medicare Part B, would require manufacturers of specified single source drugs and sole source biologics to pay incremental rebates based on international benchmark prices, with participation triggered for products meeting CMS’ spending and eligibility criteria.

The second proposal, the Guarding U.S.

Medicare Against Rising Drug Costs, or the GUARD, model for Medicare Part D, would similarly mandate manufacturer rebates for qualifying sole source drugs where the Medicare net price exceeds an MFN benchmark derived from international reference pricing methodologies.

As proposed, GLOBE would begin a five year performance period on October 1, 2026 and GUARD would begin its performance period in 2027.

These proposals will likely be subject to legal challenges that could delay their implementation or modify their impact on manufacturer pricing and revenue.

Additionally, in November 2025, CMS introduced the GENErating cost Reductions fOr U.S.

Medicaid, or the GENEROUS, Model, a voluntary MFN framework for manufacturers participating in the Medicaid Drug Rebate Program.

Although it is voluntary, the GENEROUS Model could also impact the drug pricing landscape for manufacturers.

The effect of these healthcare reform initiatives on our business and the pharmaceutical industry in general is not yet known, but could be substantial and materially adverse to our ability to successfully commercialize our product candidates at profitable price points.

Individual states have also been increasingly active in passing legislation and implementing regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraint, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.

In addition, regional health care authorities and individual hospitals are increasingly using bidding procedures to determine what pharmaceutical products and which supplies will be included in their prescription drug and other health care programs.

We expect that additional state and federal healthcare reform measures will be adopted in the future, any of which could limit the amounts that federal and state governments will pay for healthcare products and services.

European Union Approval Process

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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.

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.

PRIME Designation in the EU

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Many benefits accrue to sponsors of product candidates with PRIME designation, including but not limited to, early and proactive regulatory dialogue with the EMA, frequent discussions on clinical trial designs and other development program elements, and accelerated MAA assessment once a dossier has been submitted.

Importantly, a dedicated contact and rapporteur from the EMA’s CHMP, or Committee for Advanced Therapies, are appointed early in PRIME scheme facilitating increased understanding of the product at EMA’s Committee level.

Importantly, a dedicated contact and a rapporteur from the EMA’s Committee for Medicinal Products for Human Use ("CHMP") are appointed early in the PRIME scheme facilitating increased understanding of the product at EMA’s committee level;

for advanced therapy medicinal products, the Committee for Advanced Therapies ("CAT") is also involved.

A kick-off meeting initiates these relationships and includes a team of multidisciplinary experts at the EMA to provide guidance on the overall development and regulatory strategies.

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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).

The centralized procedure provides for the grant of a single marketing authorization by the European Commission that is valid across the EEA.

The centralized procedure provides for the grant of a single marketing authorization by the European Commission that is valid throughout the EEA.

Pursuant to Regulation (EC) No 726/2004, the centralized procedure is compulsory for specific products, including for medicines produced by certain biotechnological processes, products designated as orphan medicinal products, advanced therapy medicinal products ( i.e.

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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”.

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;

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;

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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.

• 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.

Direct-to-consumer advertising of prescription medicines is prohibited across the EU.

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The European Commission introduced legislative proposals in April 2023 that, if implemented, will replace the current regulatory framework in the EU for all medicines (including those for rare diseases and for children).

The European Commission has provided the legislative proposals to the European Parliament and the European Council for their review and

approval and in April 2024, the European Parliament proposed amendments to the legislative proposals.

Once the European Commission’s legislative proposals are approved (with or without amendment), they will be adopted into EU law.

In April 2024, the European Parliament adopted its position on the legislative proposals and, in June 2025, the Council of the European Union adopted its position.

A common position on the text has been agreed upon on December 11, 2025, in the context of

subsequent inter-institutional trilogue negotiations.

The proposed revisions remain to be adopted into EU law, and are not expected to become applicable before 2028.

Data Protection Regulation in the European Economic Area and United Kingdom

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Brexit and the Regulatory Framework in the United Kingdom

The UK formally left the EU on January 31, 2020.

As a result of the Northern Ireland Protocol, following Brexit, the EMA remained responsible for approving novel medicines for supply in Northern Ireland under the EU centralized procedure, and a separate authorization was required to supply the same medicine in Great Britain (England, Wales and Scotland).

A new framework named the Windsor Framework was approved by the EU-UK Joint Committee on March 24, 2023, and the medicines aspects of the Windsor Framework have applied since January 1, 2025.

This new framework fundamentally changes the previous system under the Northern Ireland Protocol, including with respect to the regulation of medicinal products in the UK.

The MHRA is now responsible for approving all medicinal products destined for the UK market (i.e., Great Britain and Northern Ireland) and the EMA no longer has any role in approving medicinal products destined for Northern Ireland under the EU centralized procedure.

A single UK-wide marketing authorization will be granted by the MHRA for all novel medicinal products to be sold in the UK, enabling products to be sold in a single pack and under a single authorization throughout the UK.

Following the end of the Brexit transition period on January 1, 2021 and the implementation of the Windsor Framework on January 1, 2025, the UK is not generally subject to EU laws in respect to medicines.

The EU laws that have been transposed into UK law through secondary legislation remain applicable in the UK, however, new legislation such as the EU Clinical Trials Regulation is not applicable in the UK.

As of January 1, 2021, the Medicines and Healthcare products Regulatory Agency, or MHRA, is the UK’s standalone medicines and medical devices regulator.

From January 1, 2025, under the Windsor Framework, the MHRA regulates medicines through UK-wide marketing authorizations, including for Northern Ireland.

However, although a separate authorization is now required to market medicinal products in the UK, under an international recognition procedure which was put in place by the MHRA on January 1, 2024, the MHRA may take into account decisions on the approval of a marketing authorization from the EMA (and certain other regulators) when considering an application for a UK marketing authorization.

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The criteria are essentially the same, but have been tailored for the UK market, i.e., the prevalence of the condition in the UK (rather than the EU) must not be more than five in 10,000.

Should an orphan designation be granted, the period of market exclusivity will be set from the date of first approval of the product in the UK.

Should an orphan designation be granted, the product will be entitled to up to 10 years of market exclusivity, which will be set from the date of first approval of the product in the UK.

Pricing Decisions for Approved Products

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Reference pricing used by various EU Member States, and parallel trade, i.e., arbitrage between low-priced and high-priced EU Member States, can further reduce prices.

There can be no assurance that any country that has price controls or reimbursement limitations for pharmaceutical products will allow favorable reimbursement and pricing arrangements for any products, if approved in those countries.

There can be no assurance that any

country that has price controls or reimbursement limitations for pharmaceutical products will allow favorable reimbursement and pricing arrangements for any products, if approved in those countries.

Rest of the World Regulation

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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.

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:

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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.

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 therapy to currently available therapies or so-called health technology assessments, in order to obtain reimbursement or pricing approval.

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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.

Our human capital is integral to helping us achieve our goal to end the suffering caused by endocrine conditions and neurodegenerative diseases.

The objectives for our human capital resources include, as applicable, identifying, recruiting, retaining, incentivizing and integrating our existing and additional employees.

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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.

We also maintain a website at www.amylyx.com.

We make available, free of charge, in the Investors section of our website, documents we file with or furnish to the SEC, including our Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and any exhibits and amendments to those reports.

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Our commitment to audacity, curiosity, engagement, accountability, and authenticity compels us to be responsible members of the global community.

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.

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.

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.

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.

Through our procurement department, we request information on our suppliers’ practices and their commitment to sustainability.

In 2024, we adopted a Supplier Code of Conduct.

Through our procurement department, we request information on our suppliers’ practices and their commitment to sustainability, and we expect our suppliers to adhere to our Supplier Code of Conduct (or their own code, if it is substantially similar).

This code, which is posted on our corporate website, is an extension of Amylyx’s Code of Business Conduct & Ethics and summarizes the legal obligations and ethical standards that we expect our suppliers to comply with.

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.

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.

We also expect our suppliers to operate in a responsible and efficient manner to minimize adverse impacts on the environment, including by conserving natural resources, engaging in reuse and recycling programs, and avoiding the use of hazardous materials where possible.

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We’ve seen how heightened awareness and collaboration in partnership with the community and advocacy partners ignites innovation.

With the growing availability of new

treatments, research, and technologies, we are dedicated to leading this movement in neurodegenerative and endocrine diseases.

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.

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For example, disease journeys may begin with the common problem of obtaining a correct diagnosis – for some, this takes years.

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.

benefit in drug development.

Taking into consideration the complex ecosystem of addressing unmet medical needs allows us to focus on those areas where we can make the greatest impact.

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As we advance novel drug candidates in our pipeline, we will attempt to ensure equal access for all to clinical trials and, in particular, we will attempt to conduct clinical trials comprised of a diverse set of people impacted by the disease.

We conduct our clinical trials in accordance with relevant “Good Practices” guidelines (e.g., GCP, GLP, GMP), all applicable laws and regulations, and industry standards.

We require all partners (e.g., clinical research organizations, manufacturers, and other suppliers) and clinical trial sites to comply with the same guidelines, laws, regulations and high standards.

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.

We care deeply about supporting and investing in our people, and we strive to provide clear information on our policies, practices, and benefits to all employees.

Employee benefits are an important part of total rewards, and we’re pleased to offer a comprehensive package to enable our employees’ best work and help support their health, family, and way of life.

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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.

In addition to the competitive benefits above, we offer:

• Hybrid Work Environment:

• 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:

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Recognizes employees beyond just the day-to-day

• “Take It As You Need It” Paid Time Off:

• Flexible Paid Time Off:

Paid time off designed with flexibility for vacation, personal needs, school events, or appointments

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Our board of directors is responsible for overseeing the business and management of the Company.

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

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 website.

We have an independent chairman, and five of our seven board members are independent.

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

What changed 10-K

Item 1. Business