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 endocrine conditions and neurodegenerative diseases. 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 AMX0114 in ALS. In addition, we are collaborating with Gubra A/S, an industry leader in peptide-based drug discovery, to develop a novel long-acting GLP-1 receptor antagonist. We expect to make a decision on a potential development candidate in the next few months, and pending a candidate nomination, expect to initiate Investigational New Drug (IND)-enabling studies.

Current wording

We are a clinical-stage pharmaceutical company with a mission to develop and advance novel therapies for communities with high unmet medical needs. We have preclinical and clinical development programs underway in endocrine conditions and neurodegenerative diseases. 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. We are currently developing four investigational therapies for potential impact across several diseases: avexitide in PBH, AMX0035 in Wolfram syndrome, AMX0114 in ALS, and AMX0318 in PBH and other rare diseases.

Previous wording

Our lead investigational asset is avexitide, a first-in-class inhibitor of glucagon-like peptide-1, or GLP-1, receptor activity. 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).

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 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 for congenital HI, and Orphan Drug Designation for the treatment of hyperinsulinemic hypoglycemia.

Previous wording

PBH is a condition that is estimated to affect about 160,000 people in the U.S., or 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 (or RYGB surgery). Currently, there are no FDA-approved therapies for PBH. PBH is thought to be caused by an excessive GLP-1 response, leading to hypoglycemia and impaired quality of life. Clinical manifestations can include impaired cognition, loss of consciousness, and seizures. Avexitide is designed to bind to the GLP-1 receptor on pancreatic islet beta cells and inhibit the effects of excessive GLP-1 in PBH, mitigating hypoglycemia by decreasing insulin secretion and stabilizing blood glucose levels.

Current wording

PBH is a chronic metabolic 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, or RYGB, (approximately 160,000 people in the U.S.). PBH is thought to be driven by an exaggerated GLP-1 response, primarily in response to food intake, leading to persistent, recurrent, and often debilitating rapid drops in blood glucose, known as hypoglycemia. The American Diabetes Association recognizes hypoglycemia as a potential medical emergency because low blood glucose levels can compromise the body’s ability to maintain essential physiologic processes. In addition, hypoglycemia in the context of PBH may manifest as neuroglycopenia – an inadequate supply of glucose to the brain, which can cause confusion, cognitive dysfunction, loss of consciousness, and seizures. PBH can be associated with substantial disability, compromising safety, disrupting independent living, and affecting nutritional status and overall quality of life. Despite the substantial burden, there are currently no FDA-approved therapies for PBH.

Previous 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. We expect to complete recruitment in the first quarter of 2026, with topline data expected in the third quarter of 2026. We continue to expect to commercially launch avexitide in 2027, if approved.

Current wording

LUCIDITY (NCT06747468) is a 78-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 were 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, a 16-week double-blind treatment period, and an open-label extension (OLE) period with a duration of 32 weeks. The primary efficacy objective of LUCIDITY is to evaluate the FDA-agreed upon 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. Enrollment for LUCIDITY was completed in March 2026. We continue to expect to announce topline data in the third quarter of 2026, and if approved, a commercial launch in 2027.

Previous 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.

Current 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.

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, or PK, profile maintaining exposure in the therapeutic range through 24 hours, supporting once daily dosing.

Current 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 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). 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.

Previous 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.

Current wording

Avexitide was generally well-tolerated, with a favorable safety profile replicated across the five previous 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.

Previous wording

In addition, new exploratory analyses from the Phase 2 PREVENT and Phase 2b clinical trials of avexitide were presented at the Endocrine Society’s annual meeting in July 2025. In the Phase 2b trial, avexitide 90 mg once daily, the dose being evaluated in the pivotal Phase 3 LUCIDITY trial, led to a 64% least-squares mean reduction (p=0.0031) vs. 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. Consistent reductions in composite rate of Level 2 and Level 3 hypoglycemic events also were seen with avexitide 45 mg twice daily studied in the Phase 2b trial and avexitide 30 mg twice daily and 60 mg once daily studied in the Phase 2 PREVENT trial. New PK and pharmacodynamic, or PD, data were also presented, demonstrating continuous pharmacologic activity of the 90 mg once daily dose regimen for a 24-hour period.

Current wording

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.

Previous wording

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

Current wording

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.

Previous 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.

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

Previous 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.

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 and premature mortality. Wolfram syndrome is most commonly caused by pathogenic variants in Wolfram syndrome type 1 gene, or WFS1. Because of the clear link between WFS1 mutations and ER stress, Wolfram syndrome is considered a prototypical ER stress disorder. Wolfram syndrome affects approximately 3,000 people living in the U.S., and there are currently no FDA-approved treatment options.

Previous wording

The majority of people with Wolfram syndrome carry mutations in the WFS1 gene, which encodes a protein called wolframin that spans the membrane of the ER. Loss of wolframin function leads to ER stress and impaired mitochondrial dynamics, which lead to multi-organ cell dysfunction and death – starting with beta cells in the pancreas, then neurons in the visual system, auditory system, and throughout the body. Because of the clear link between WFS1 mutations and ER stress, Wolfram syndrome is considered a prototypical ER stress disorder. AMX0035 is hypothesized to mitigate cell death in Wolfram syndrome by reducing ER stress and mitochondrial dysfunction. In preclinical models, treatment with AMX0035 improved WFS1 protein expression, increased insulin secretion, and inhibited beta cell death in cells derived from people with Wolfram syndrome. AMX0035 also prevented cell death in neuronal cells derived from people with Wolfram syndrome and significantly delayed progression of the diabetes phenotype in a WFS1-knock-out preclinical model.

Current wording

In preclinical models, treatment with AMX0035 improved WFS1 protein expression, increased insulin secretion, and inhibited beta cell death in cells derived from people with Wolfram syndrome. AMX0035 also prevented cell death in neuronal cells derived from people with Wolfram syndrome and significantly delayed progression of the diabetes phenotype in a WFS1-knock-out preclinical model.

Previous 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.

Current wording

In October 2024, we announced positive topline 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. 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.

Previous wording

Treatment with AMX0035 at Week 24 and at Week 48 also showed sustained improvements or stabilization in glycemic control, as measured by hemoglobin A1c (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. Safety data were consistent with safety data from prior studies of AMX0035. All AEs were mild or moderate, and there were no serious AEs related to AMX0035 treatment. The analysis performed at Week 24 included 11 participants in the Per Protocol population with genetically confirmed Wolfram syndrome (one participant was excluded from the Per Protocol population due to not meeting the study inclusion criteria of genetically confirmed Wolfram syndrome) and 12 participants in the Intent-to-Treat population. Long-term data at Week 48 included 10 participants in the Per Protocol population with genetically confirmed Wolfram syndrome and 11 participants in the Intent-to-Treat population. One participant discontinued between Week 24 and Week 48 for reasons unrelated to safety.

Current wording

In May 2025, we announced positive data from HELIOS at Week 48. Consistent with the HELIOS trial’s previously presented primary efficacy outcome of improvement in pancreatic function (as described above), 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.

Previous 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.

Current wording

AMX0114 is an investigational antisense oligonucleotide, or ASO, targeting calpain-2, or CAPN2, with FDA Fast Track Designation for the potential treatment of ALS. Decades of scientific literature and published data demonstrate 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. One of the ways ALS progresses is through axonal degeneration, which disrupts neural connectivity and contributes significantly to disease pathology. 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 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. 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. In September 2025, we fully enrolled cohort 1 (n=12) and expect to present early cohort data at the 36th International Symposium on ALS/MND held from December 5-7. Based on biomarker collection and analysis timelines, we anticipate biomarker data will be available in the coming months and expect to present these at a medical meeting in the first half of 2026.

Current wording

The Phase 1 LUMINA clinical trial (NCT06665165) is a multinational, randomized, double-blind, placebo-controlled, multiple ascending dose trial evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of AMX0114 in people living with ALS. LUMINA will also assess change from baseline in calpain-2 levels, NfL levels, and other pharmacodynamic biomarkers of ALS. LUMINA is anticipated to enroll approximately 48 adult participants. Participants will be randomized 3:1 to receive AMX0114 or placebo by intrathecal administration once every four weeks for a total of up to four doses. We completed enrollment of Cohort 1 (n=12) of LUMINA in September 2025 and completed enrollment of Cohort 2 (n=12) in March 2026.

Previous wording

Research and development expenses consist primarily of costs incurred in connection with the research and development of avexitide, AMX0035, AMX0114 and other potential future product candidates. We expense research and development costs as incurred. These expenses include:

Current wording

Research and development expenses consist primarily of costs incurred in connection with the research and development of avexitide, AMX0035, AMX0114, AMX0318 and other potential future product candidates. We expense research and development costs as incurred. These expenses include:

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 third 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 and AMX0318, primarily due to the increased size and duration of later-stage clinical trials and related product manufacturing expenses. 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, AMX0318 and any future product candidates. Our clinical development costs may vary significantly based on factors such as:

Previous wording

The successful development and commercialization of avexitide, AMX0035, AMX0114 and any other current or future product candidates is highly uncertain, due to the numerous risks and uncertainties associated with product development and commercialization, including the following:

Current wording

The successful development and commercialization of avexitide, AMX0035, AMX0114, AMX0318 and any other current or future product candidates is highly uncertain, due to the numerous risks and uncertainties associated with product development and commercialization, including the following:

Previous 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.

Current wording

A change in the outcome of any of these variables with respect to the development of avexitide, AMX0035, AMX0114, AMX0318 or any other current or future product candidates could have a significant impact on the cost and timing associated with the development of our product candidates. We may never succeed in obtaining or maintaining, as applicable, regulatory approval for avexitide, AMX0035, AMX0114, AMX0318 or any other current or future product candidates.

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 and nine months ended September 30, 2025 as compared to the three and nine months ended September 30, 2024. However, we expect that selling, 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. We expect that selling, general and administrative expenses will continue to increase in future periods as we continue to increase headcount, advance our clinical pipeline, and incur significant costs related to our pre-commercialization activities as we prepare for potential near term regulatory approvals.

Previous wording

We have historically not incurred significant income taxes. We continue to maintain a full valuation allowance against all of our deferred tax assets based on management’s evaluation of all available evidence, including our history of incurring significant losses from operations. As a result, we don’t expect to incur material income taxes for the foreseeable future.

Current wording

We have historically not incurred significant income taxes. We continue to maintain a full valuation allowance against all of our deferred tax assets based on management’s evaluation of all available evidence, including our history of incurring significant losses from operations. As a result, we do not expect to incur material income taxes for the foreseeable future.

Previous wording

Research and development expenses were $19.9 million for the three months ended September 30, 2025, compared to $21.2 million for the three months ended September 30, 2024. The decrease was primarily due to a $1.9 million decrease in expenses related to AMX0035 for the treatment of PSP after its discontinuation and a $4.1 million decrease in spending on AMX0035 for the treatment of ALS following the topline data from the PHOENIX trial. The decrease was offset by a $4.8 million increase in expenses related to the pivotal Phase 3 LUCIDITY clinical trial in PBH and other costs related to avexitide.

Current wording

Research and development expenses were $27.6 million for the three months ended March 31, 2026, compared to $22.1 million for the three months ended March 31, 2025. The increase was primarily due to a $4.6 million increase in expenses related to the pivotal Phase 3 LUCIDITY clinical trial in PBH and other costs related to avexitide, and a $4.2 million increase in expenses related to other programs. Other programs includes milestone payments totaling $4.0 million made to Gubra following the selection and handover of AMX0318 as a development candidate for PBH and other rare diseases during the three months ended March 31, 2026. The increase was offset by a $3.9 million decrease in expenses related to AMX0035 for the treatment of PSP after its discontinuation.

Previous wording

Selling, general and administrative expenses were $16.2 million for the three months ended September 30, 2025 compared to $17.8 million for the three months ended September 30, 2024. The decrease was primarily due to a decrease of $2.1 million in other expenses and a decrease of $0.8 million in consulting and professional services. The decrease was partially offset by an increase of $1.2 million in payroll and personnel-related costs. The decrease in other expenses is primarily due to lower facilities and IT-related expenses. 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 increase in payroll and personnel-related costs was primarily driven by an increase in stock-based compensation.

Current wording

Selling, general and administrative expenses were $16.2 million for the three months ended March 31, 2026 compared to $15.7 million for the three months ended March 31, 2025. The increase was primarily due to an increase of $0.7 million in consulting and professional services, partially offset by a decrease of $0.2 million in other expenses. The increase in consulting and professional services is primarily due to an increase in commercial and marketing activity as we prepare for a potential commercial launch of avexitide, if approved, as well as increased spend for general legal services. The decrease in other expenses is primarily due to lower facilities and IT-related expenses.

Previous wording

As of September 30, 2025, we had cash, cash equivalents and marketable securities of $344.0 million and an accumulated deficit of $718.4 million. We believe our existing cash, cash equivalents and marketable securities as of September 30, 2025 will be sufficient to fund our operations into 2028. We have based this estimate on assumptions that may prove to be wrong, and we could exhaust our available capital resources sooner than we expect.

Current wording

As of March 31, 2026, we had cash, cash equivalents and marketable securities of $279.8 million and an accumulated deficit of $792.7 million. We believe our existing cash, cash equivalents and marketable securities as of March 31, 2026 will be sufficient to fund our operations into 2028. We have based this estimate on assumptions that may prove to be wrong, and we could exhaust our available capital resources sooner than we expect.

Previous 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.

Current 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.

Previous 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:

Current wording

Despite the decline in research and development and general administrative expenses in 2025 as compared to 2024, we expect our expenses to increase in connection with our ongoing activities, particularly as we advance the preclinical activities, manufacturing and clinical trials of avexitide, AMX0035, AMX0114, AMX0318 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 expect 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

seek to identify and develop, acquire or in-license additional product candidates;

Current wording

seek to identify and develop, acquire or in-license additional product candidates or other assets;

Previous wording

the scope, progress, results and costs of drug discovery, laboratory testing, preclinical and clinical development for avexitide, AMX0035, AMX0114 and any future product candidates;

Current wording

the scope, progress, results and costs of drug discovery, laboratory testing, preclinical and clinical development for avexitide, AMX0035, AMX0114, AMX0318 and any future product candidates;

Previous wording

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

Current wording

the costs, timing and outcome of regulatory review of avexitide, AMX0035, AMX0114, AMX0318 and any future product candidates;

Previous 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;

Current wording

timing delays with respect to preclinical and clinical development of avexitide, AMX0035, AMX0114, AMX0318 and any future product candidates, including as result of any future outbreak of any highly infectious or contagious diseases;

Previous wording

During the nine months ended September 30, 2024, operating activities used $108.6 million of cash, primarily resulting from our net loss of $264.2 million, $8.1 million net accretion of discounts on investments and $19.1 million of net cash used by changes in our operating assets and liabilities, offset by $118.7 million of inventory impairment and loss on firm purchase commitments and $26.3 million of non-cash stock-based compensation expense. Our net loss non-cash adjustments also include $36.2 million of acquired IPR&D assets, which are classified as investing activities.

Current wording

During the three months ended March 31, 2026, operating activities used $36.9 million of cash, primarily resulting from our net loss of $41.3 million, $0.6 million net accretion of discounts on investments, and $5.3 million of net cash used by changes in our operating assets and liabilities, offset by $6.1 million of non-cash stock-based compensation expense and a $4.0 million charge for in-process research and development, or IPR&D, milestones related to the Gubra collaboration.

Previous wording

Net cash used by changes in our operating assets and liabilities primarily consisted of a $5.4 million decrease in accrued expenses and a $1.2 million decrease in operating lease liabilities, offset by a $3.3 million decrease in prepaid expenses and other current assets and a $1.4 million decrease in operating ROU assets.

Current wording

Net cash used by changes in our operating assets and liabilities primarily consisted of a $6.7 million decrease in accrued expenses and a $0.3 million decrease in operating lease liabilities, offset by a $1.4 million decrease in prepaid expenses and other current assets and a $0.3 million decrease in operating right-of-use assets.

Previous wording

During the nine months ended September 30, 2025, operating activities used $95.4 million of cash, primarily resulting from our net loss of $111.7 million, $4.5 million net accretion of discounts on investments, and $1.2 million of net cash used by changes in our operating assets and liabilities, offset by $21.3 million of non-cash stock-based compensation expense.

Current 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.

Previous wording

Net cash used by changes in our operating assets and liabilities primarily consisted of a $38.3 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 $33.4 million in accrued expenses and a $20.6 million decrease in accounts payable.

Current 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.

Previous wording

During the nine months ended September 30, 2024, net cash provided by investing activities was $10.7 million, resulting primarily from $279.0 million of investments that matured, offset by $232.0 million of purchases of marketable securities and a $36.2 million cash outflow to acquire IPR&D assets related to the avexitide asset acquisition.

Current wording

During the three months ended March 31, 2026, net cash provided by investing activities was $36.3 million, resulting primarily from $60.0 million of investments that matured, offset by $19.7 million of purchases of marketable securities and $4.0 million in IPR&D milestone payments related to the Gubra collaboration.

Previous wording

During the nine months ended September 30, 2025, net cash used in investing activities was $15.4 million, resulting primarily from $201.4 million of purchases of marketable securities, offset by $186.0 million of investments that matured.

Current 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.

Previous wording

During the nine months ended September 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.

Current wording

During the three months ended March 31, 2026, net cash provided by financing activities was $3.2 million. This amount consisted of $3.2 million of proceeds from exercises of stock options and vesting of stock awards, net of withholding taxes paid on stock-based awards.

Previous wording

During the nine months ended September 30, 2025, net cash provided by financing activities was $257.2 million. This amount consisted primarily of $65.5 million in proceeds from the January 2025 Offering, net of offering costs paid, and $191.1 million in proceeds from the September 2025 Offering, net of offering costs paid.

Current 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.