Amylyx Pharmaceuticals, Inc.
For the period ended Mar 31, 2025. Filed May 8, 2025.
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A company's report for each of its first three quarters. The financial statements are not audited. It shows how the business has moved since the last annual report, and what management says changed.
Mar 31, 2025 · Filed May 8, 2025
AMLX$29.50+6.8%Stored close · as of Nov 6, 2026
What changed in Management’s Discussion and Analysis?
Read the current filingPrevious report: 10-Q
Period ended 2024-09-30; filed 2024-11-07.
0000950170-24-122833
Item 2. Management’s Discussion and Analysis of Financial Condition and Results of OperationsCurrent report: 10-Q
Period ended 2025-03-31; filed 2025-05-08.
0000950170-25-066363
Item 2. Management’s Discussion and Analysis of Financial Condition and Results of OperationsThe baseline is this issuer’s latest earlier reporting period of the same form that was filed before the current report. A previous 10-Q is a different quarter, not a year-over-year comparison. Amendments are excluded.
Compared 158 previous paragraphs and 134 current paragraphs.
74 unchanged; 38 reworded; 19 added; 41 removed; 5 previous and 3 current paragraphs rearranged.
Tables are not compared: 6 previous and 3 current tables excluded. Dates, whitespace, punctuation and numbering changes are ignored; changes to financial figures remain significant.
A changed paragraph is not evidence that risk increased or decreased. An unchanged paragraph does not establish that risk stayed the same.
Added paragraphs (19)
Current report
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 report
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 report
LUCIDITY was informed by data from five clinical trials of avexitide in people with PBH showing consistent, dose-dependent effects across studies. The five clinical trials include a Phase 1 trial, a single ascending dose trial, a multiple ascending dose trial, and two Phase 2 trials:
Current report
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 report
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 report
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.
Current report
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 report
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 report
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 report
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 report
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 report
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 report
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. AMX0114 was generally well tolerated in in vivo preclinical safety studies.
Current report
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 report
Research and Development Expenses
Current report
Selling, General and Administrative Expenses
Current report
Research and Development Expenses
Current report
Selling, General and Administrative Expenses
Current report
In January 2025, we entered into an underwriting agreement with Leerink Partners LLC relating to the issuance and sale of an aggregate of 19,714,285 shares of our common stock, which includes the exercise in full by the underwriter of its option to purchase an additional 2,571,428 shares, or the January 2025 Offering. The public offering price per share was $3.50. The January 2025 Offering resulted in proceeds of approximately $65.5 million, net of underwriting discounts and offering expenses.
Removed paragraphs (41)
Previous report
We are a biotechnology company committed to the discovery and development of new treatment options for communities with high unmet needs, including people living with serious and fatal diseases. We have preclinical and clinical development programs underway in neurodegenerative diseases and endocrine conditions. Our pipeline of programs includes avexitide for the treatment of hyperinsulinemic hypoglycemia, AMX0035 for the treatment of Wolfram syndrome, AMX0035 for the treatment of progressive supranuclear palsy, or PSP, and AMX0114, our antisense oligonucleotide targeting calpain-2 for the treatment of amyotrophic lateral sclerosis, or ALS.
Previous report
AMX0035 is a specially formulated oral fixed-dose combination of sodium phenylbutyrate, or PB, and taurursodiol, or TURSO, developed to target a broad range of neurodegenerative diseases. AMX0035 was developed by Amylyx and is designed to mitigate neurodegeneration by simultaneously targeting endoplasmic reticulum, or ER, stress and mitochondrial dysfunction, two connected central pathways that lead to cell death and neurodegeneration. We have shown in multiple models that AMX0035 can keep neurons alive under a variety of different conditions and stresses. These conditions includein vitro models of neurodegeneration, ER stress, mitochondrial dysfunction, oxidative stress and various other disease-specific models, as well asin vivo models of ALS, Wolfram syndrome, Alzheimer’s disease, or AD, and multiple sclerosis, or MS. Trials of AMX0035 in AD and ALS have shown the ability to reduce markers associated with neurodegenerative diseases in clinical trials, including a reduction of tau, a key protein aggregate shared across several neurodegenerative diseases, and YKL-40, a marker of neuroinflammation, respectively.
Previous report
The safety profile of AMX0035 has been well established in clinical trials and post-marketing surveillance. Thousands of adults have been treated with AMX0035 whether through clinical trials across several neurodegenerative conditions and in post-approval settings. AMX0035 has been generally well-tolerated and the most common adverse reactions were gastrointestinal side effects (e.g. diarrhea, nausea, constipation, decreased appetite, abdominal pain, flatulence), occurring more often in the first 3 weeks of treatment and were generally nonserious. The benefit-risk balance of AMX0035 remains favorable for ongoing clinical development programs.
Previous report
Wolfram syndrome is a rare, progressive monogenic disease caused by mutations in the WFS1 gene that cause ER stress and mitochondrial dysfunction, leading to multi-organ cell dysfunction and death. We believe Wolfram syndrome impacts approximately 3,000 people in the U.S. Researchers from the Washington University School of Medicine in St. Louis, in collaboration with Amylyx, published preclinical data exploring the potential of AMX0035 as a novel therapeutic approach for Wolfram syndrome in the peer-reviewed Journal of Clinical Investigation Insight. These data showed that AMX0035 had the ability to dampen the impact of ER stress and mitochondrial dysfunction across patient-derived beta cells and neurons impacted by WFS1 mutations, and thereby potentially stabilizing and in some cases improving cellular functioning and viability. Amylyx announced that the FDA granted orphan drug designation to AMX0035 for the treatment of Wolfram syndrome in November 2020.
Previous report
HELIOS showed improvements in its primary endpoint of C-peptide response with a change from baseline to Week 24 at 120 minutes of +3.8 minutesng/mL (minng/mL) [standard error (SE): 19.3] in the Intent to Treat group (N=12) and +20.2 min*ng/mL [SE: 11.2] in the Per Protocol group (N=11). In addition, as outlined in the table below, participants receiving AMX0035 had improved glycemic control, as measured by markers of glucose metabolism; improved visual acuity in some participants, as measured by the Snellen chart; and improvement or stabilization of the disease, as measured by the Clinician Reported Global Impression of Change (CGIC) and Patient Reported Global Impression of Change (PGIC).
Previous report
† Upon genetic review, one participant did not meet the inclusion/exclusion criteria for HELIOS. This participant was found to have an autosomal recessive mutation confirmed to be pathogenic on just one of the two alleles and variant of uncertain significance on the other allele. This participant was within normal range for C-peptide, glycemic measures, and vision suggesting lack of typical Wolfram syndrome phenotype. Data presented with and without this participant who reached Week 24 (Intent to Treat and Per Protocol, respectively).
Previous report
†† In non-diabetic individuals, C-peptide peaks after a meal at approximately ~30 minutes; in Wolfram syndrome, peak is slower but generally was at or before 120 minutes in HELIOS. Area under the curve (AUC) over 120 minutes after meal challenge reflects beta cell response to a meal. Amylyx is currently planning to focus on 120-minute AUC as the C-peptide measure for future studies.
Previous report
††† HELIOS defines a “responder” on both the CGIC and PGIC as no change or improvement given the progressive nature of Wolfram syndrome.
Previous report
The primary efficacy endpoint of the trial measures change from baseline in C-peptide, an established, objective laboratory measure of pancreatic beta cell function and glycemic control, was assessed using a Mixed Meal Tolerance Test at Week 24. Secondary and exploratory outcomes include the measurement of other diabetic responses and other domains affected by the disease. The safety profile of AMX0035 was consistent with that observed in other populations in which the drug has been extensively studied. We are engaging with stakeholders, including the FDA, and planning for a single Phase 3 clinical trial and will share additional details on the clinical trial design once finalized.
Previous report
We are pursuing AMX0035 for the treatment of PSP based on AMX002’smechanism, preclinical data, and the tau reduction seen in the Phase 2 PEGASUS trial of AMX0035 in AD. These data were published in the peer-reviewed medical journal Alzheimer’s & Dementia: Translational Research & Clinical Interventions, a journal of the Alzheimer’s Association, in August 2024. PSP is a rare neurodegenerative disorder that affects body movements, walking, balance and eye movement and is characterized by widespread neurodegeneration associated with tau protein deposition in subcortical regions of the brain. Based on in vitro, in vivo and clinical data, AMX0035 may influence tau pathology, a key hallmark in people living with PSP. Genetic evidence indicates that a risk factor for PSP may be the unfolded protein response activated in disease-affected regions of the brain. PB has been shown to upregulate and recruit chaperone proteins, stabilize protein folding, and reduce ER stress and the unfolded protein response, while TURSO has been shown to inhibit tau phosphorylation induced by metabolic stress. In addition to preclinical data on PB and TURSO individually, PB and TURSO combined have shown a synergistic effect in targeting the hallmark pathways of neurodegeneration to simultaneously prevent or slow neuronal cell death. There are currently no approved therapies for the treatment of PSP, and the disease is reported to affect seven in 100,000 people worldwide.
Previous report
The ORION trial, a Phase 2b/3 global trial of AMX0035 for the treatment of PSP, remains ongoing. The primary efficacy endpoint of the ORION trial evaluates disease progression as measured by the rate of change on the 28-item Progressive Supranuclear Palsy Rating Scale (PSPRS), total score at Week 52, an established and validated endpoint in PSP clinical trials. Secondary efficacy endpoints are disease progression as measured by a modified 10-item PSPRS score and motor aspects of activities of daily life as measured by the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part 2 (MDS-UPDRS Part II). Exploratory outcomes include changes in activities of daily living, cognitive function, quality of life, overall survival, brain regional volumes, fluid biomarkers of neuronal injury/inflammation, and caregiver burden. Safety and tolerability will be evaluated by assessing the frequency of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs). Data from an interim analysis of the ORION study of AMX0035 in PSP are expected in mid-2025.
Previous report
Additionally, we remain steadfast in our commitment to the ALS community. ALS is a disorder characterized by motor neuron degeneration in the motor cortex and spinal cord that leads to progressive muscle weakness. Unlike most other cells in the body that regularly die and are replaced as part of healthy function, mature central nervous system (CNS) neurons are normally resistant to cell death and generally cannot regenerate. There are approximately 30,000 people living with ALS in the U.S. ALS is a disease that affects people regardless of background, and there are approximately 200,000 people living worldwide with ALS.
Previous report
To that end, we have completed the IND-enabling studies of AMX0114, a potent antisense oligonucleotide targeting inhibition of Calpain-2, a key contributor to the axonal (also known as Wallerian) degeneration pathway. Axonal degeneration has been recognized as an important early contributor to the clinical presentation and pathogenesis of ALS and other neurodegenerative diseases. Calpain-2 is considered an essential protein in the process of axonal degeneration and has been repeatedly linked to neurofilament biology in published studies. Preclinical studies completed to date have shown that AMX0114 can achieve potent, dose-dependent, and durable knockdown of CAPN2 mRNA expression and Calpain-2 protein levels in human motor neurons. Moreover, in preclinical efficacy studies, treatment with AMX0114 reduced extracellular neurofilament light chain levels following neurotoxic insult in induced pluripotent stem cell (iPSC)-derived human motor neurons, and improved survival of iPSC-derived human motor neurons harboring ALS-linked, pathogenic TDP-43 mutations. Neurofilament is a broadly researched biomarker in ALS.
Previous report
In ALS, we received clearance from Health Canada for our Clinical Trial Application for AMX0114 in people living with ALS. We plan to begin the Phase 1 multiple ascending dose, placebo-controlled trial called LUMINA in Canada by the end of 2024 or in early 2025. We will evaluate safety and the biological activity in approximately 48 adults living with ALS and evaluate four dose levels, starting with 12.5 mg. We presented our plans for the study at the Northeast ALS Consortium Annual Meeting last month.
Previous report
We also submitted an Investigational New Drug application to the FDA for AMX0114. The FDA restricted dosing to an amount that is lower than the Company's proposed starting dose of 12.5 mg and has requested additional information, which resulted in a clinical hold. Toxicology data from studies showed a greater than 10X safety margin at the starting dose of 12.5 mg based on the no observed adverse effect level (NOAEL) determined by independent toxicology firms. We are working to address FDA comments. We believe the trial can be completed outside of the U.S if needed. We expect early cohort data from LUMINA in 2025.
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On April 4, 2024, we announced we had started a process with the FDA and Health Canada to voluntarily discontinue the marketing authorizations for RELYVRIO®/ALBRIOZA™ (sodium phenylbutyrate and taurursodiol [also known as ursodoxicoltaurine]; also known as AMX0035) for the treatment of ALS and remove the product from the market in the U.S. and Canada, or the “RELYVRIO®/ALBRIOZA™Discontinuation. This decision was informed by topline results from the global Phase 3 PHOENIX trial, which failed to meet its prespecified primary and secondary endpoints, engagement with regulatory authorities, and discussions with the ALS community. As of April 4, 2024, RELYVRIO/ALBRIOZA was no longer available for new patients. Patients who were currently on therapy in the U.S. and Canada who, in consultation with their physician, wished to stay on treatment had the option to be transitioned to a free drug program. Patients and their physicians were informed that final shipments of free drug were shipped to allow treatment through early 2025. The NDA is now on the Discontinued Drug Product List of the Orange Book. We will continue to collect available data on survival and to share learnings from PHOENIX to help inform future ALS research. We wound down the Open Label Extension as planned.
Previous report
We will continue to incur significant expenses as we advance avexitide, AMX0035, AMX0114 and advance or acquire any future product candidates through preclinical and clinical development, setup and initiate additional trials, hire additional clinical, scientific, management and administrative personnel, seek regulatory approval and pursue commercialization of any approved product candidates. We may also incur expenses related to business development activities, such as in-licensing of product candidates.
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Product Revenue, Net
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Product revenue, net recognized during the three and nine months ended September 30, 2024 and 2023 primarily relates to units of ALBRIOZA and RELYVRIO sold in Canada and the U.S., respectively. In April 2024, we announced we had started a process with the FDA and Health Canada to voluntarily discontinue the marketing authorizations for RELYVRIO®/ALBRIOZA™and remove the product from the market in the U.S. and Canada based on topline results from the global Phase 3 PHOENIX trial. As a result, we will not generate revenue from the sale of RELYVRIO®/ALBRIOZA™ in future periods.
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Cost of Sales
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Cost of sales consists primarily of costs associated with the manufacturing of RELYVRIO, ALBRIOZA, certain period costs and losses on purchase commitments with contract manufacturing organizations. Following our announcement of a process to discontinue the marketing authorizations for RELYVRIO®/ALBRIOZA™ and remove the product from the market in the U.S. and Canada, we will not report product cost of sales in future periods.
Previous report
Acquired in-process research and development, or IPR&D, expenses include consideration for the purchase of substantially all the assets and interests in the development, manufacture and commercialization of avexitide from Eiger.
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Restructuring Expenses
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Restructuring expense consists primarily of employee severance and termination benefits, contract termination costs, impairment of long-lived assets and other costs. We records cost and liabilities associated with exit and disposal activities in accordance with FASB ASC Topic 420, Exit or Disposal Cost Obligations. Such costs are based on estimates of fair value in the period liabilities are incurred. We evaluate and adjust these costs as appropriate for changes in circumstances as additional information becomes available.
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On July 9, 2024, we completed the Eiger Acquisition. During the three months ended September 30, 2024, we recorded a charge of approximately $36.2 million associated with the acquired in-process research and development assets of avexitide with no alternative future use.
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Research and development expenses were $21.2 million for the three months ended September 30, 2024, compared to $30.0 million for the three months ended September 30, 2023. The decrease was primarily due to a $9.5 million decrease in spending on AMX0035 for the treatment of ALS following the topline data from the PHOENIX trial, and a $4.3 million decrease in payroll and personnel-related primarily related to a decrease in the number of employees as a result of the Restructuring Plan. The decrease in research and development expenses was offset by a $3.4 million increase in spending on AMX0035 for the treatment of PSP and a $1.6 million increase in other costs. The increase in spending on AMX0035 for the treatment of PSP was primarily related to costs to support the continuation of the ORION Phase 2b/3 global clinical trial, and the increase in other costs were primarily due to an increase in preclinical development activities.
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Provision for Income Taxes
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We recorded an income tax provision of zero and $1.5 million for the three months ended September 30, 2024 and 2023, respectively. The absence of an income tax provision for the three months ended September 30, 2024 was driven by the estimated effective tax rate for the year. The income tax benefit for the three months ended September 30, 2023 was primarily driven by the estimated annual effective tax rate for the year, as well as discrete income tax benefit of $0.1 million.
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Comparison of the nine months ended September 30, 2024 and 2023
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Product Revenue, Net
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Product revenue, net was $88.0 million for the nine months ended September 30, 2024, compared to $272.3 million for the nine months ended September 30, 2023. During these periods, product revenue, net was primarily related to units of RELYVRIO and ALBRIOZA sold in the U.S. and Canada, respectively. As a result of the RELYVRIO®/ALBRIOZA™Discontinuation, we did not generate significant revenue from product sales in the second or third quarters of 2024.
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Cost of Sales
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On July 9, 2024, the Company completed the Eiger Acquisition. During the nine months ended September 30, 2024, the Company recorded a charge of approximately $36.2 million associated with the acquired in-process research and development assets of avexitide with no alternative future use.
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Restructuring Expenses
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During the nine months ended September 30, 2024, restructuring expenses were approximately $22.9 million which includes employee severance and termination benefits of approximately $21.9 million, contract termination costs, impairment of long-lived assets and other costs of $1.0 million. We substantially completed the Restructuring Plan in the second quarter of 2024.
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Provision for Income Taxes
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We recorded an income tax provision of $0.2 million and an income tax benefit of $3.3 million for the nine months ended September 30, 2024 and 2023, respectively. The income tax provision for the nine months ended September 30, 2024 was driven by discrete income tax expense of $0.2 million. The income tax benefit for the nine months ended September 30, 2023 was primarily driven by the estimated effective tax rate for the year, as well as discrete income tax benefit of $0.5 million.
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In the second half of 2022, we began generating revenue from the sale of our approved drug product RELYVRIO, known as ALBRIOZA in Canada. In April 2024, we announced the RELYVRIO®/ALBRIOZA™ Discontinuation. We also announced the Restructuring Plan, which was designed to focus our resources on key clinical and preclinical programs and included a reduction in force which reduced our workforce by approximately 70% and decreased external financial commitments outside of our priority areas. We completed the Restructuring Plan in the second half of 2024. To date, we have financed our operations primarily through revenue from the sale of our approved products, the sale and issuance of common stock, convertible preferred stock and convertible notes. As of September 30, 2024, we had cash, cash equivalents and marketable securities of $234.4 million.
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Comparison of the nine months ended September 30, 2024 and 2023
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Contractual Obligations and Commitments
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Reworded paragraphs (38)
Previous wording
Avexitide, an investigational, first-in-class glucagon-like peptide-1, or GLP-1, receptor antagonist, has been evaluated in five clinical trials for post-bariatric hypoglycemia, or PBH, and has also been studied in congenital hyperinsulinism, or HI, two indications characterized by hyperinsulinemic hypoglycemia. The U.S. Food and Drug Administration, or FDA, has granted avexitide breakthrough therapy designation for both indications, rare pediatric disease designation in congenital HI, and orphan drug designation for the treatment of hyperinsulinemic hypoglycemia (which includes PBH and congenital HI). Avexitide is designed to bind to the GLP-1 receptor on pancreatic islet beta cells and block the effect of GLP-1 to mitigate hypoglycemia by decreasing insulin secretion and stabilizing glucose levels. In PBH, an indication with no approved treatment options impacting approximately 160,000 people in the U.S., excessive GLP-1 can lead to the hypersecretion of insulin and subsequent severe hypoglycemia events, including autonomic and neuroglycopenic symptoms if left unaddressed. Avexitide was generally well tolerated, with a favorable safety profile replicated across five clinical trials in people with PBH.
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 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.
Previous wording
In previous Phase 2 and Phase 2b studies in PBH, avexitide showed statistically significant reductions in hypoglycemia events characterized by low blood glucose, including severe hypoglycemia events with altered mental and/or physical function requiring assistance. FDA guidance for industry in diabetes combined with initial FDA feedback specific to the pivotal Phase 3 program of avexitide for PBH suggest that reduction in hypoglycemia events could be an endpoint to support approval following positive results from a pivotal Phase 3 clinical trial. We expect to begin a Phase 3 program for avexitide in PBH in the first quarter of 2025 with topline data anticipated in 2026. We are actively engaging in discussions with the broader congenital HI community to develop a path forward.
Current wording
In congenital HI, we are actively engaging in discussions with the broader congenital HI community to develop a path forward.
Previous wording
We are investigating AMX0035 in neurodegenerative diseases and endocrine conditions where ER stress and mitochondrial dysfunction are implicated, including PSP and Wolfram syndrome.
Current 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.
Previous wording
On October 17, 2024, we announced positive topline data from the HELIOS trial, an ongoing, open-label Phase 2 study designed to evaluate if AMX0035 slows progression of diabetic, visual, and other measures in people living with Wolfram syndrome and to evaluate safety and tolerability. HELIOS showed improvement in pancreatic 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. Patient- and physician-reported global impressions of change showed disease stability or improvement in all participants, meeting prespecified responder criteria. 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 analysis performed includes Week 24 data for all 12 participants and data for all participants who completed their Week 36 (n=10) and Week 48 (n=6) assessments as of the data cutoff.
Current 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.
Previous wording
Research and development expenses consist primarily of costs incurred in connection with the research and development of AMX0035, avexitide, 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 and other potential future product candidates. We expense research and development costs as incurred. These expenses include:
Previous wording
expenses incurred under agreements with CROs, contract manufacturing organizations, or CMOs, as well as investigative sites and consultants that conduct our clinical trials, preclinical studies and other scientific development services;
Current wording
expenses incurred under agreements with CROs, CMOs, as well as investigative sites and consultants that conduct our clinical trials, preclinical studies and other scientific development services;
Previous wording
Certain of our indirect research and development expenses are not tracked on an indication-by-indication basis for AMX0035. We do not allocate employee costs and facilities, including depreciation or other indirect costs, to specific indications because these costs are deployed across multiple indications and, as such, are not separately classified. We use internal resources to oversee the research and discovery as well as to manage our preclinical development, process development, manufacturing and clinical development activities. These employees work across multiple indications and, therefore, we do not track their costs by indication.
Current wording
Certain of our indirect research and development expenses are not tracked on an indication-by-indication basis. We do not allocate employee costs and facilities, including depreciation or other indirect costs, to specific indications because these costs are deployed across multiple indications and, as such, are not separately classified. We use internal resources to oversee the research and discovery as well as to manage our preclinical development, process development, manufacturing and clinical development activities. These employees work across multiple indications and, therefore, we do not track their costs by indication.
Previous wording
Research and development activities are central to our business model. Product candidates such as 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. 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 AMX0035, avexitide 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, 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:
Previous wording
The successful development and commercialization of AMX0035, avexitide 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 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
the availability of drug substance and drug product for use in production of AMX0035 or other product candidates;
Current wording
the availability of drug substance and drug product for use in production of avexitide, AMX0035 or other product candidates;
Previous wording
obtaining and maintaining third-party insurance coverage and adequate reimbursement for any approved products;
Current wording
obtaining and maintaining third-party insurance coverage and adequate reimbursement in the future for any approved products;
Previous wording
A change in the outcome of any of these variables with respect to the development of AMX0035, avexitide 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 AMX0035, avexitide 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 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.
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, compliance with Section 404 of the Sarbanes-Oxley Act, or Section 404, 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 the Restructuring Plan designed to focus our resources on key clinical and preclinical programs. The restructuring included a reduction in force which is expected to reduce our workforce by approximately 70% and a decrease in external financial commitments outside our priority areas. As a result, we anticipate that our selling, general and administrative expenses will decrease in 2024 as compared to 2023.
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 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.
Previous wording
Income taxes are determined using the asset and liability approach. Deferred tax assets and liabilities represent future tax consequences of temporary differences between the financial statement carrying amounts and the tax basis of assets and liabilities and for tax attribute carryforwards using enacted tax rates expected to be in effect in the years in which the differences reverse. Realization of our deferred tax assets is dependent upon the generation of future taxable income, the amount and timing of which are uncertain. Valuation allowances are provided, if, based upon the weight of available evidence, it is more likely than not that some or all of the deferred tax assets will not be realized. 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 don’t expect to incur material income taxes for the foreseeable future.
Previous wording
As a result of the RELYVRIO®/ALBRIOZA™ Discontinuation, we did not generate significant revenue from product sales for the three months ended September 30, 2024 and the balance primarily represents gross-to-net adjustments reflecting actual rebate and return activity during the period. For the three months ended September 30, 2023, product revenue, net was primarily related to units of RELYVRIO and ALBRIOZA 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 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.
Previous wording
Cost of sales were $124.6 million for the nine months ended September 30, 2024, compared to $16.1 million for the nine months ended September 30, 2023. During these periods, cost of sales consisted of costs to procure, manufacture and distribute our marketed products, RELYVRIO and ALBRIOZA. As a result of the RELYVRIO®/ALBRIOZA™Discontinuation, the Company recorded approximately $118.7 million of charges associated with the write-down of inventory and losses on firm purchase commitments for the nine months ended September 30, 2024.
Current 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.
Previous wording
Research and development expenses were $81.2 million for the nine months ended September 30, 2024, compared to $83.3 million for the nine months ended September 30, 2023. The slight decrease was primarily due to a $16.3 million decrease in spending on AMX0035 for the treatment of ALS following the topline data from the PHOENIX trial, and a $0.9 million decrease in payroll and personnel-related costs related to a decrease in the number of employees as a result of the Restructuring Plan. The decrease in research and development expenses was offset by a $9.5 million increase in spending on AMX0035 for the treatment of PSP and a $5.6 million increase in other costs due to an increase in preclinical development activities. The increase in spending on AMX0035 for the treatment of PSP was primarily related to costs to support the continuation of the ORION Phase 2b/3 global clinical trial.
Current 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.
Previous wording
Selling, general and administrative expenses were $17.8 million for the three months ended September 30, 2024 compared to $48.7 million for the three months ended September 30, 2023. The decrease was primarily due to a decrease of $14.5 million in payroll and personnel-related costs, a decrease of $10.7 million in consulting and professional services and a decrease of $5.7 million in other expenses. The decrease in payroll and personnel-related costs was primarily related to a decrease in the number of employees as a result of the Restructuring Plan. 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 decrease in activity to wind down commercial operations.
Current 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.
Previous wording
As of September 30, 2024, we had cash, cash equivalents and marketable securities of $234.4 million. In April 2024, we announced a restructuring to focus our financial resources on upcoming clinical milestones. Under the restructuring, we reduced our workforce by approximately 70% and decreased external financial commitments outside of our priority areas. We believe that with these changes, our existing cash, cash equivalents and marketable securities as of September 30, 2024, will be sufficient to meet our anticipated operating and capital expenditure requirements for at least one year from the issuance of this Quarterly Report. We have based this estimate on assumptions that may prove to be wrong, and we could exhaust our available capital resources sooner than we expect. See “Liquidity and Capital Resources” below.
Current 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.
Previous wording
Since inception, we have devoted a substantial amount of our efforts to research and development and pre-commercialization and commercialization activities, including recruiting management and technical staff, raising capital, producing materials for preclinical studies and clinical trials, and building infrastructure to support such activities. As of September 30, 2024, we have funded our operations primarily through public offerings of our common stock, private sales of preferred stock, convertible notes, and through revenue from sales of RELYVRIO and ALBRIOZA in the U.S. and Canada, respectively.
Current wording
Since inception, we have devoted substantially all of our efforts to research and development, pre-commercialization and commercialization activities, including recruiting management and technical staff, raising capital, producing materials for preclinical studies and clinical trials, and building infrastructure to support such activities. As of March 31, 2025, we have funded our operations primarily through public offerings of our common stock, private sales of preferred stock, convertible notes, and through revenue from sales of RELYVRIO and ALBRIOZA in the U.S. and Canada, respectively, between July 2022 and April 2024.
Previous wording
We expect to incur significant expenses in connection with our ongoing activities, particularly as we advance the preclinical activities, manufacturing and clinical trials of AMX0035, avexitide and any other current or future product candidates or acquire or in-license additional product candidates or products. In addition, we expect to continue to incur 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 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:
Previous wording
continue our research and development efforts of avexitide in PBH and conduct clinical trials of avexitide;
Current wording
continue our research and development efforts of avexitide in PBH, or any other indications, and conduct clinical trials of avexitide;
Previous wording
continue our research and development efforts, including our ongoing Phase 3 trial of AMX0035 in PSP and our ongoing Phase 2 trial of AMX0035 for the treatment of Wolfram syndrome;
Current wording
continue our research and development efforts of AMX0035, including our ongoing Phase 2b/3 trial of AMX0035 in PSP and our ongoing Phase 2 trial of AMX0035 for the treatment of Wolfram syndrome;
Previous wording
continue to develop AMX0114, antisense oligonucleotide, for the treatment of people living with ALS;
Current wording
continue to develop AMX0114, our antisense oligonucleotide, including our ongoing Phase 1 clinical trial of AMX0114 for the treatment of ALS;
Previous wording
develop the necessary processes, controls and manufacturing data to obtain additional marketing approval for AMX0035 or approval for any future product candidates and to support manufacturing on a commercial scale;
Current wording
develop the necessary processes, controls and manufacturing data to obtain marketing approval for current or future product candidates and to support manufacturing on a commercial scale;
Previous wording
seek additional regulatory approvals for AMX0035 or approvals for any future product candidates that successfully complete clinical trials, if any;
Current wording
seek regulatory approvals for any current or future product candidates that successfully complete clinical trials, if any;
Previous wording
the scope, progress, results and costs of drug discovery, laboratory testing, preclinical and clinical development for AMX0035, avexitide 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 and any future product candidates;
Previous wording
the costs, timing and outcome of regulatory review of AMX0035, avexitide and any future product candidates;
Current wording
the costs, timing and outcome of regulatory review of avexitide, AMX0035 and any future product candidates;
Previous wording
timing delays with respect to preclinical and clinical development of AMX0035, avexitide 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 and any future product candidates, including as result of any future outbreak of any highly infectious or contagious diseases;
Previous wording
Until such time, if ever, that we can generate product revenue sufficient to resume and sustain profitability, we may finance our cash needs through equity offerings, debt financings, government or other third-party funding, marketing and distribution arrangements and other collaborations, strategic alliances and licensing arrangements. To the extent that we raise additional capital through the sale of common stock, convertible securities or other equity securities, current ownership interests will be diluted. If we raise additional funds through collaborations or marketing, distribution or licensing arrangements with third parties, we may have to relinquish valuable rights to our technologies, future revenue streams or product candidates or grant licenses on terms that may not be favorable to us. In addition, debt financing, if available, may result in fixed payment obligations and may involve agreements that include restrictive covenants that limit our ability to take specific actions, such as incurring additional debt, making capital expenditures, creating liens, redeeming stock or declaring dividends, that could adversely impact our ability to conduct our business. If we are unable to raise additional funds when needed, we may be required to delay, limit, reduce or terminate our product development or future commercialization efforts or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves.
Current wording
Until such time, if ever, that we can generate product revenue sufficient to sustain profitability, we may finance our cash needs through equity offerings, debt financings, government or other third-party funding, marketing and distribution arrangements and other collaborations, strategic alliances and licensing arrangements. To the extent that we raise additional capital through the sale of common stock, convertible securities or other equity securities, current ownership interests will be diluted. If we raise additional funds through collaborations or marketing, distribution or licensing arrangements with third parties, we may have to relinquish valuable rights to our technologies, future revenue streams or product candidates or grant licenses on terms that may not be favorable to us. In addition, debt financing, if available, may result in fixed payment obligations and may involve agreements that include restrictive covenants that limit our ability to take specific actions, such as incurring additional debt, making capital expenditures, creating liens, redeeming stock or declaring dividends, that could adversely impact our ability to conduct our business. If we are unable to raise additional funds when needed, we may be required to delay, limit, reduce or terminate our product development or future commercialization efforts or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves.
Previous wording
During the nine months ended September 30, 2023, operating activities used $1.6 million of cash, primarily resulting from our net income of $44.5 million and $27.6 million of non-cash stock-based compensation expense, offset by $7.4 million net accretion of discounts on investments and $67.2 million of net cash used by changes in our operating assets and liabilities.
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 in our operating assets and liabilities primarily consisted of a $46.6 million increase in inventory capitalized during the period, a $14.0 million increase in accounts receivable, net, and a $7.6 million increase in prepaid expenses and other current assets.
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, 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, 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.
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 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.
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, 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, 2023, net cash provided by investing activities was $71.1 million, resulting primarily from $246.2 million of investments that matured, partially offset by $174.2 million of purchases of marketable securities during the period.
Current 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.
Previous wording
During the nine months ended September 30, 2023, net cash provided by financing activities was $3.3 million. This amount consisted primarily of $3.4 million of proceeds from exercises of stock options and vesting of stock awards, net of employee taxes paid on these awards.
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.
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, 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.
Rearranged current paragraphs (3)
Current report — wording carried from elsewhere
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.
Current report — wording carried from elsewhere
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 report — wording carried from elsewhere
Comparison of the three months ended March 31, 2025 and 2024
Rearranged previous paragraphs (5)
Previous report — wording carried elsewhere
Cost of sales for the three months ended September 30, 2024 were primarily related to losses on firm purchase commitments. For the three months ended September 30, 2023, cost of sales consisted of costs to procure, manufacture and distribute units of RELYVRIO and ALBRIOZA in the U.S. and Canada.
Previous report — wording carried elsewhere
The following table summarizes our results of operations for the periods presented (in thousands):
Previous report — wording carried elsewhere
The following table summarizes our research and development expenses for the nine months ended September 30, 2024 and 2023 (in thousands):
Previous report — wording carried elsewhere
Selling, general and administrative expenses were $97.2 million for the nine months ended September 30, 2024 compared to $136.1 million for the nine months ended September 30, 2023. The decrease was primarily due to a decrease of $23.1 million in payroll and personnel-related costs and a decrease of $14.9 million in consulting and professional services, offset by an increase of $0.9 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 increase in other expenses is primarily due to an increase in spending for operations as a public company and other expenses.
Previous report — wording carried elsewhere
Based on our current operational plans and assumptions, we believe that our existing cash, cash equivalents, and marketable securities, will be sufficient to meet our anticipated operating and capital expenditure requirements for at least twelve months after the date of the filing of this Quarterly Report. We have based these estimates on assumptions that may prove to be wrong, and we could utilize our available capital resources sooner than we expect.