Amylyx Pharmaceuticals, Inc.

Previous wording

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. 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. We are currently developing three investigational therapies for potential impact across several diseases: avexitide in PBH and congenital hyperinsulinism, or HI, AMX0035 in Wolfram syndrome and PSP, and AMX0114 in ALS.

Current wording

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. 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. We are currently developing three investigational therapies for potential impact across several diseases: avexitide in PBH, AMX0035 in Wolfram syndrome and PSP, and AMX0114 in ALS.

Previous wording

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 HI, two indications characterized by hyperinsulinemic hypoglycemia. The U.S. Food and Drug Administration, or the FDA, has granted avexitide Breakthrough Therapy Designation for both PBH and congenital HI, Rare Pediatric Disease Designation in congenital HI, and Orphan Drug Designation for the treatment of hyperinsulinemic hypoglycemia.

Current wording

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 HI, two indications characterized by hyperinsulinemic hypoglycemia. The U.S. Food and Drug Administration, or the FDA, has granted avexitide Breakthrough Therapy Designation for both PBH and congenital HI, Rare Pediatric Disease Designation in congenital HI, and Orphan Drug Designation for the treatment of hyperinsulinemic hypoglycemia (which includes PBH and congenital HI).

Previous wording

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. 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. Safety and tolerability will also be evaluated. In April 2025, we announced that the first participant had been dosed. 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.

Current wording

In April 2025, we dosed the first participant for the pivotal Phase 3 LUCIDITY clinical trial for avexitide in PBH following RYGB surgery. 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 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. 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. 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 is anticipated in 2027.

Previous wording

In the Phase 2 (PREVENT), 28-day, randomized, placebo-controlled crossover trial (N=18), results showed a significant reduction in rates of Level 2 and 3 hypoglycemic events in participants with PBH after RYGB surgery following treatment with 30 mg twice daily and 60 mg once daily of avexitide compared with placebo. PREVENT’s primary endpoint was met with statistical significance, showing both avexitide dosing regimens improved the lowest glucose level (nadir) after a meal as measured during formal mixed meal tolerance testing, or MMTT. Mean plasma glucose nadir was increased by 21% (p=0.001) and 26% (p=0.0002) following avexitide 30 mg twice daily and 60 mg once daily dosing, respectively, compared to placebo. Avexitide was generally well tolerated. The most common adverse events, or AEs, were injection site bruising, headache, and nausea; these occurred more often with placebo than either avexitide dose. No participants withdrew due to AEs.

Current wording

In the Phase 2 (PREVENT), 28-day, randomized, blinded, placebo-controlled crossover trial (N=18), results showed a significant reduction in rates of Level 2 and 3 hypoglycemic events in participants with PBH after RYGB surgery following treatment with 30 mg twice daily and 60 mg once daily of avexitide compared with placebo. PREVENT’s primary endpoint was met with statistical significance, showing both avexitide dosing regimens improved the lowest glucose level (nadir) after a meal as measured during formal mixed meal tolerance testing, or MMTT. Mean plasma glucose nadir was increased by 21% (p=0.001) and 26% (p=0.0002) following avexitide 30 mg twice daily and 60 mg once daily dosing, respectively, compared to placebo. Avexitide was generally well-tolerated. The most common adverse events, or AEs, were injection site bruising, headache, and nausea; these occurred more often with placebo than either avexitide dose. No participants withdrew due to AEs.

Previous wording

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. 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). There were no reported serious AEs, and AEs were mostly mild to moderate and resolved without medical treatment. The most common AEs included diarrhea, headache, bloating, and injection site reaction/bruising. No participant withdrew due to AEs. In the Phase 2b trial, 90 mg once daily of avexitide has also demonstrated a favorable pharmacokinetic profile maintaining exposure in the therapeutic range through 24 hours, supporting once daily dosing.

Current wording

RYGB surgery and other upper-gastrointestinal surgeries. 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). There were no reported serious AEs, and AEs were mostly mild to moderate and resolved without medical treatment. The most common AEs included diarrhea, headache, bloating, and injection site reaction/bruising. No participant withdrew due to AEs. In the Phase 2b trial, 90 mg once daily of avexitide has also demonstrated a favorable pharmacokinetic, or PK, profile maintaining exposure in the therapeutic range through 24 hours, supporting once daily dosing.

Previous wording

Avexitide was generally well tolerated, with a favorable safety profile replicated across five clinical trials in people with PBH. In addition, avexitide demonstrated a clear GLP-1 antagonist pharmacodynamic effect, including lowering insulin and raising the glucose nadir, in healthy volunteers.

Current wording

Avexitide was generally well-tolerated, with a favorable safety profile replicated across five clinical trials in people with PBH. In healthy volunteers, avexitide demonstrated a clear GLP-1 antagonist PD effect, including lowering insulin and raising the glucose nadir.

Previous wording

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 ALS.

Current wording

In addition to avexitide, we are investigating AMX0035, an oral, fixed-dose combination of sodium phenylbutyrate and taurursodiol in Wolfram syndrome and PSP, and AMX0114, an antisense oligonucleotide targeting calpain-2 in ALS.

Previous wording

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.

Current wording

AMX0035 is designed to slow or mitigate neurodegeneration by targeting endoplasmic reticulum, or ER stress, and mitochondrial dysfunction, two connected central pathways that lead to 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.

Previous wording

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.

Current wording

Wolfram syndrome is a rare, monogenic, progressive neurodegenerative disorder 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.

Previous wording

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. 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. Similar overall improvements or stabilization were observed across all secondary endpoints, including hemoglobin A1c (HbA1c), time in target glucose range assessed by continuous glucose monitoring, and visual acuity. 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. 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 May 2025. Data from participants at Week 48 and ongoing discussions with the FDA will inform the design of a Phase 3 trial of AMX0035 in Wolfram syndrome.

Current wording

In October 2024, we announced positive topline data, including the primary efficacy outcome of the trial, from the Phase 2 open-label HELIOS clinical trial of AMX0035 in 12 adults living with Wolfram syndrome, and in May 2025, we announced positive long-term data from the HELIOS trial of AMX0035 in Wolfram syndrome through Week 48. HELIOS (NCT05676034) is a single-site, single-arm, open-label, Phase 2 trial designed to evaluate the safety and tolerability of AMX0035, as well as its effects on 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 measured by C-peptide response to a mixed-meal tolerance test at Week 24, treatment with AMX0035 through Week 48 demonstrated continued and sustained improvement in pancreatic beta cell function, in contrast to the expected decrease in pancreatic function with disease progression.

Previous wording

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 approximately 23,000 in the United States. Currently, there are 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.

Current wording

PSP is a rare, progressive, and fatal neurodegenerative disease that can affect movement, gait, balance, cognition, eye movements, swallowing, and speech and is estimated to affect 23,000 people in the U.S. People living with PSP have a life expectancy of six to eight years after symptom onset. There are no approved therapies for PSP. PSP is a tauopathy, which is defined by the buildup of tau protein in the brain. Based on its prior effect from a Phase 2 trial of AMX0035 in reducing tau in cerebrospinal fluid, or CSF, in people with Alzheimer’s disease, we believe AM00X35 is the first brain- and cell-penetrant agent that has demonstrated a significant tau reduction in CSF to be tested in PSP.

Previous wording

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, an established and validated endpoint in PSP clinical trials. Safety and tolerability will also be evaluated. We completed enrollment in the Phase 2b portion of the ORION trial in January of this year, with a total of 139 participants randomized. Efficacy and safety data from an unblinded 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.

Current wording

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 a Phase 2b/3 clinical trial 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, an established and validated endpoint in PSP clinical trials. Safety and tolerability will also be evaluated. We completed enrollment in the Phase 2b portion of the ORION trial in January 2025, with a total of 139 participants randomized. Efficacy and safety 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.

Previous wording

AMX0114 is an investigational antisense oligonucleotide, targeting calpain-2, or CAPN2. Decades of scientific literature and published data demonstrated that CAPN2, a protein involved in neurofilament biology, plays an essential role in axonal degeneration, which is a critical effector in the progression of various neurodegenerative diseases including ALS. ALS is a relentlessly progressive and fatal neurodegenerative disorder caused by motor neuron death in the brain and spinal cord. Motor neuron loss in ALS leads to deteriorating muscle function, the inability to move and speak, respiratory paralysis, and, eventually, death. ALS is defined as a rare disease, but it affects as many as 30,000 adults in the U.S. and 3,000 in Canada. The most common form of the disease is sporadic ALS, with more than 90% of people with ALS showing no clear family history.

Current wording

AMX0114 is an investigational antisense oligonucleotide designed to target calpain-2, a calcium-activated protease. The FDA has granted AMX0114 Fast Track designation for the treatment of ALS. Peer-reviewed research has demonstrated that overactive calpain-2 activity may be an important driver of disease progression in ALS and other neurodegenerative diseases by executing the degeneration of axons, the long tubular neuronal segments which carry signals from neurons to the muscle or other neurons. ALS is a relentlessly progressive and fatal neurodegenerative disorder caused by motor neuron death in the brain and spinal cord. Motor neuron loss in ALS leads to deteriorating muscle function, the inability to move and speak, respiratory paralysis, and eventually, death. ALS is defined as a rare disease, but it affects as many as 30,000 adults in the U.S. and 3,000 in Canada. The most common form of the disease is sporadic ALS, with more than 90% of people with ALS showing no clear family history.

Previous wording

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. In April 2025, we announced that the first participant had been dosed in Canada. We are working to open U.S. sites for screening, enrollment, and dosing. 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.

Current wording

In April 2025, we dosed the first participant in Canada for the Phase 1 LUMINA clinical trial (NCT06665165), a multicenter, randomized, double-blind, placebo-controlled, multiple ascending dose trial designed to evaluate the safety and biological activity of AMX0114 in people living with ALS. LUMINA will also assess ALS biomarkers, including change from baseline in NfL levels. In addition to the activated sites in Canada, we are continuing to open U.S. sites for screening, enrollment, and dosing. 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.

Previous wording

Research and development activities are central to our business model. 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. Despite a decline in research and development expenses in 2024 and in the first quarter of 2025 compared to prior respective periods, 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. 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 and any future product candidates. Our clinical development costs may vary significantly based on factors such as:

Current wording

Research and development activities are central to our business model. 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. Despite a decline in research and development expenses in 2024 and in the first quarter of 2025 compared to prior respective periods, research and development expenses increased in the second quarter of 2025 compared to the prior year period and we expect that our research and development expenses will continue to increase in connection with our planned clinical development activities in the near term and in the future. 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 and any future product candidates. Our clinical development costs may vary significantly based on factors such as:

Previous wording

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. We may never succeed in obtaining or maintaining, as applicable, regulatory approval for avexitide, AMX0035 or any other current or future product candidates.

Current wording

A change in the outcome of any of these variables with respect to the development of avexitide, AMX0035, AMX0114 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. We may never succeed in obtaining or maintaining, as applicable, regulatory approval for avexitide, AMX0035, AMX0114 or any other current or future product candidates.

Previous wording

Selling, general and administrative expenses consist primarily of salaries and related costs for personnel in executive, finance, sales, marketing, as well as administrative functions. Selling, general and administrative expenses also include legal fees relating to patent and corporate matters; professional fees for accounting, auditing, tax and administrative consulting services; corporate insurance costs; administrative travel expenses; sales and marketing expenses; information technology; charitable donations to independent charitable foundations; facility-related and other operating costs. In April 2024, we announced a restructuring plan, or 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 during the three months ended March 31, 2025 as compared to the three months ended March 31, 2024. However, we expect that general and administrative expenses will increase in future periods as we advance our clinical pipeline.

Current wording

Selling, general and administrative expenses consist primarily of salaries and related costs for personnel in executive, finance, sales, marketing, as well as administrative functions. Selling, general and administrative expenses also include legal fees relating to patent and corporate matters; professional fees for accounting, auditing, tax and administrative consulting services; corporate insurance costs; administrative travel expenses; sales and marketing expenses; information technology; charitable donations to independent charitable foundations; facility-related and other operating costs. In April 2024, we announced a restructuring plan, or 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 during the three and six months ended June 30, 2025 as compared to the three and six months ended June 30, 2024. However, we expect that general and administrative expenses will increase in future periods as we advance our clinical pipeline.

Previous wording

As a result of the RELYVRIO®/ALBRIOZA™ Discontinuation, we did not generate cost of sales for the three months ended March 31, 2025. Cost of sales for the three months ended March 31, 2024 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 $110.5 million of charges associated with the write-down of inventory and losses on firm purchase commitments for the three months ended March 31, 2024.

Current wording

As a result of the RELYVRIO®/ALBRIOZA™ Discontinuation, we did not generate cost of sales for the three months ended June 30, 2025. Cost of sales for the three months ended June 30, 2024 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 $7.4 million of charges associated with the write-down of inventory and losses on firm purchase commitments for the three months ended June 30, 2024.

Previous wording

As a result of the RELYVRIO®/ALBRIOZA™ Discontinuation, we did not generate revenue from product sales for the three months ended March 31, 2025. For the three months ended March 31, 2024, product revenue, net was primarily related to units of RELYVRIO and ALBRIOZA previously sold in the U.S. and Canada.

Current wording

As a result of the RELYVRIO®/ALBRIOZA™ Discontinuation, we did not generate revenue from product sales for the six months ended June 30, 2025. For the six months ended June 30, 2024, product revenue, net was primarily related to units of RELYVRIO and ALBRIOZA previously sold in the U.S. and Canada.

Previous wording

Research and development expenses were $22.1 million for the three months ended March 31, 2025, compared to $36.6 million for the three months ended March 31, 2024. The decrease was primarily due to a $13.9 million decrease in spending on AMX0035 for the treatment of ALS following the topline data from the PHOENIX trial, and a $7.1 million decrease in payroll and personnel-related costs primarily related to a decrease in the number of employees as a result of the Restructuring Plan, offset by a $5.4 million increase in expenses related to the pivotal Phase 3 LUCIDITY clinical trial for avexitide in PBH.

Current wording

Research and development expenses were $49.3 million for the six months ended June 30, 2025, compared to $60.0 million for the six months ended June 30, 2024. The decrease was primarily due to a $22.6 million decrease in spending on AMX0035 for the treatment of ALS following the topline data from the PHOENIX trial, and a $7.1 million decrease in payroll and personnel-related costs primarily related to a decrease in the number of employees as a result of the Restructuring Plan. The decrease was partially offset by a $12.5 million increase in expenses related to the pivotal Phase 3 LUCIDITY clinical trial for avexitide in PBH, a $4.0 million increase in expenses related to AMX0035 for the treatment of PSP and a $2.5 million increase in expenses related to other research and development activities.

Previous wording

Selling, general and administrative expenses were $15.7 million for the three months ended March 31, 2025 compared to $57.8 million for the three months ended March 31, 2024. The decrease was primarily due to a decrease of $16.0 million in payroll and personnel-related costs, a decrease of $12.8 million in consulting and professional services and a decrease of $13.3 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 in consulting and professional services is 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 and activity to wind down commercial operations.

Current wording

Selling, general and administrative expenses were $31.3 million for the six months ended June 30, 2025 compared to $79.4 million for the six months ended June 30, 2024. The decrease was primarily due to a decrease of $16.8 million in payroll and personnel-related costs, a decrease of $14.8 million in consulting and professional services and a decrease of $16.5 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 in consulting and professional services is 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 and activity to wind down commercial operations.

Previous wording

As of March 31, 2025, we had cash, cash equivalents and marketable securities of $204.1 million and an accumulated deficit of $642.6 million. We believe our existing cash, cash equivalents and marketable securities as of March 31, 2025 will be sufficient to meet our anticipated operating and capital expenditure requirements through 2026. 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.

Current wording

As of June 30, 2025, we had cash, cash equivalents and marketable securities of $180.8 million and an accumulated deficit of $684.0 million. We believe our existing cash, cash equivalents and marketable securities as of June 30, 2025 will be sufficient to meet our anticipated operating and capital expenditure requirements through 2026. 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.

Previous wording

We expect to finance our near-term operations through our existing cash, cash equivalents and marketable securities and if needed, the sale of equity, debt financings or other capital sources, including potential collaborations with other companies, royalty financings, or other strategic transactions. 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.

Current wording

We expect to finance our near-term operations through our existing cash, cash equivalents and marketable securities and the sale of equity, debt financings or other capital sources, including potential collaborations with other companies, royalty financings, or other strategic transactions. 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.

Previous wording

Despite the decline in research and development and general administrative expenses in 2024 as compared to 2023 and in the first quarter of 2025 as compared to the first quarter of 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 and any other current or future product candidates or acquire or in-license additional product candidates or products. We may also incur expenses related to business development activities, such as in-licensing or acquisition of product candidates. In addition, we will continue to incur additional costs associated with operating as a public company, including significant legal, accounting, investor relations and other expenses. We expect to incur significant expenses as we:

Current wording

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, AMX0114 and any other current or future product candidates or acquire or in-license additional product candidates or products. We may also incur expenses related to business development activities, such as in-licensing or acquisition of product candidates. In addition, we will continue to incur additional costs associated with operating as a public company, including significant legal, accounting, investor relations and other expenses. We expect to incur significant expenses as we:

Previous wording

continue to develop AMX0114, our antisense oligonucleotide, including our ongoing Phase 1 clinical trial of AMX0114 for the treatment of ALS;

Current wording

continue our research and development efforts of AMX0114, including our ongoing Phase 1 clinical trial of AMX0114 for the treatment of ALS;

Previous wording

the costs, timing and outcome of regulatory review of avexitide, AMX0035 and any future product candidates;

Current wording

the costs, timing and outcome of regulatory review of avexitide, AMX0035, AMX0114 and any future product candidates;

Previous wording

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;

Current wording

timing delays with respect to preclinical and clinical development of avexitide, AMX0035, AMX0114 and any future product candidates, including as result of any future outbreak of any highly infectious or contagious diseases;

Previous wording

During the three months ended March 31, 2025, operating activities used $39.8 million of cash, primarily resulting from our net loss of $35.9 million, $9.2 million of net cash used by changes in our operating assets and liabilities and $1.7 million net accretion of discounts on investments, offset by $6.8 million of non-cash stock-based compensation expense.

Current wording

During the six months ended June 30, 2025, operating activities used $65.1 million of cash, primarily resulting from our net loss of $77.4 million and $3.2 million net accretion of discounts on investments, offset by $14.2 million of non-cash stock-based compensation expense and $0.8 million of net cash provided by changes in our operating assets and liabilities.

Previous wording

Net cash used by changes in our operating assets and liabilities primarily consisted of a $0.7 million decrease in prepaid expenses and other current assets, a $1.9 million increase in accounts payable, offset by a $11.9 million decrease in accrued expenses.

Current wording

Net cash provided by changes in our operating assets and liabilities primarily consisted of a $6.5 million decrease in prepaid expenses and other current assets, and a $1.1 million decrease in operating ROU assets, offset by a $6.5 million decrease in accrued expenses and a $1.2 million decrease in operating lease liabilities.

Previous wording

During the three months ended March 31, 2024, operating activities used $0.5 million of cash, primarily resulting from our net loss of $118.8 million and $2.6 million net accretion of discounts on investments, offset by $110.5 million of inventory impairment and loss on firm purchase commitments, $9.9 million of non-cash stock-based compensation expense and $0.2 million of net cash provided by changes in our operating assets and liabilities.

Current wording

During the six months ended June 30, 2024, operating activities used $67.1 million of cash, primarily resulting from our net loss of $191.5 million, $5.8 million net accretion of discounts on investments and $8.5 million of net cash used by changes in our operating assets and liabilities, offset by $117.9 million of inventory impairment and loss on firm purchase commitments and $19.5 million of non-cash stock-based compensation expense.

Previous wording

Net cash provided by our operating assets and liabilities primarily consisted of a $19.7 million decrease in accounts receivable, net, offset by a $9.3 million increase in inventory capitalized during the period, a $2.1 million increase in prepaid expenses and other current assets, a decrease of $7.8 million in accrued expenses and a $0.7 million decrease in accounts payable.

Current wording

Net cash used by changes in our operating assets and liabilities primarily consisted of a $36.0 million decrease in accounts receivable, net, offset by a $9.3 million increase in inventory capitalized during the period, net of inventory written-off, a decrease of $20.3 million in accrued expenses and a $17.1 million decrease in accounts payable.

Previous wording

During the three months ended March 31, 2025, net cash used in investing activities was $43.7 million, resulting primarily from $103.6 million of purchases of marketable securities, offset by $60.0 million of investments that matured.

Current wording

During the six months ended June 30, 2025, net cash used in investing activities was $20.7 million, resulting primarily from $142.6 million of purchases of marketable securities, offset by $122.0 million of investments that matured.

Previous wording

During the three months ended March 31, 2024, net cash provided by investing activities was $0.8 million, resulting primarily from $74.0 million of investments that matured, partially offset by $73.1 million of purchases of short-term investments during the period.

Current wording

During the six months ended June 30, 2024, net cash used in investing activities was $28.1 million, resulting primarily from $232.0 million of purchases of short-term investments during the period, offset by $204.0 million of investments that matured.

Previous wording

During the three months ended March 31, 2025, net cash provided by financing activities was $65.7 million. This amount consisted primarily of $65.6 million in proceeds from the January 2025 Offering, net of offering costs paid.

Current wording

During the six months ended June 30, 2025, net cash provided by financing activities was $65.6 million. This amount consisted primarily of $65.6 million in proceeds from the January 2025 Offering, net of offering costs.

Previous wording

During the three months ended March 31, 2024, net cash provided by financing activities was $0.1 million. This amount consisted primarily of $0.1 million of proceeds from exercises of stock options and vesting of stock awards, net of withholding taxes paid on stock-based awards.

Current wording

During the six months ended June 30, 2024, net cash provided by financing activities was $0.2 million. This amount consisted primarily of $0.2 million of proceeds from exercises of stock options and vesting of stock awards, net of withholding taxes paid on stock-based awards.