Amylyx Pharmaceuticals Inc
For the period ended Sep 30, 2024. Filed Nov 7, 2024.
View on SEC.govAbout this filing
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.
Sep 30, 2024 · Filed Nov 7, 2024
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 2024-06-30; filed 2024-08-08.
0000950170-24-093311
Item 2. Management’s Discussion and Analysis of Financial Condition and Results of OperationsCurrent 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 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 152 previous paragraphs and 158 current paragraphs.
106 unchanged; 38 reworded; 13 added; 5 removed; 3 previous and 1 current paragraphs rearranged.
Tables are not compared: 5 previous and 6 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 (13)
Current report
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 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).
Current 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).
Current 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.
Current report
††† HELIOS defines a “responder” on both the CGIC and PGIC as no change or improvement given the progressive nature of Wolfram syndrome.
Current 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.
Current 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.
Current report
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.
Current report
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.
Current report
Comparison of the nine months ended September 30, 2024 and 2023
Current report
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.
Current report
incur expenses in preparation for commercialization for any approved product candidates related to product sales, marketing, manufacturing, and distribution;
Current report
Comparison of the nine months ended September 30, 2024 and 2023
Removed paragraphs (5)
Previous report
Comparison of the six months ended June 30, 2024 and 2023
Previous report
execute the announced Restructuring Plan or any future restructurings; and
Previous report
the length and results of negotiations with contract manufacturing organizations;
Previous report
Comparison of the six months ended June 30, 2024 and 2023
Previous report
We recognized a loss on purchase commitments of $7.4 million and $25.3 million for the three and six months ended June 30, 2024, respectively, which was recorded to cost of sales on the condensed consolidated statement of operations and as part of accrued expenses on the condensed consolidated balance sheet. The purchase commitment loss is based on an estimate of future commitments related to supply agreements with third party vendors for which we do not expect to have related sales.
Reworded paragraphs (38)
Previous wording
We are a biotechnology company that is 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, neuroendocrine and endocrine diseases. 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.
Current wording
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 wording
On July 9, 2024, we completed the acquisition of substantially all the assets and interests in the development, manufacture and commercialization of avexitide from Eiger BioPharmaceuticals, Inc., Eiger or the Seller, for $35.1 million, subject to final adjustment. Avexitide is an investigational, first-in-class glucagon-like peptide-1, or GLP-1, receptor antagonist that has been evaluated in five clinical trials for post-bariatric hypoglycemia (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 hypoglycemic 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
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.
Previous wording
In previous Phase 2 and Phase 2b studies in PBH, avexitide showed statistically significant reductions in hypoglycemic events characterized by low blood glucose, including severe hypoglycemic 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 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.
Previous wording
We are investigating AMX0035 in neurodegenerative and neuroendocrine diseases where ER stress and mitochondrial dysfunction are implicated, including PSP and Wolfram syndrome.
Current wording
We are investigating AMX0035 in neurodegenerative diseases and endocrine conditions where ER stress and mitochondrial dysfunction are implicated, including PSP and Wolfram syndrome.
Previous wording
Wolfram syndrome is a rare, progressive genetic 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.
Current wording
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 wording
In April 2024, we announced interim 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. The interim analysis performed was based on a data cutoff as of March 5, 2024 and included all participants who completed their Week 24 assessments as of the cutoff (n=8). 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, assessed using a Mixed Meal Tolerance Test (MMTT). Secondary and exploratory outcomes include the measurement of other diabetic responses and other domains affected by the disease. The interim data from eight participants who received 24 weeks of treatment demonstrated that AMX0035 had a clinically meaningful effect on key outcomes including preliminary overall improvement in glucose control measures, visual acuity measures and disease burden in adult participants living with Wolfram syndrome, where disease progression was expected. The safety profile of AMX0035 was consistent with that observed in other populations in which the drug has been extensively studied. We plan to present the HELIOS topline data from the HELIOS trial for all 12 participants at Week 24, including all of the longer-term data available for participants who have reached their Week 36 or Week 48 visit at that time, at a medical meeting this fall. 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.
Current wording
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 wording
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. We are pursuing this indication based on AMX0035’s mechanism, preclinical data, and the tau reduction seen in the Phase 2 PEGASUS trial of AMX0035 in AD.
Current wording
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 wording
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. We are moving forward with our plans and are preparing to initiate a multiple ascending dose clinical trial of AMX0114 in people living with ALS in the second half of 2024.
Current wording
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 wording
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. 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. We will continue to collect available data on survival and to share learnings from PHOENIX to help inform future ALS research. We are planning to wind down the Open Label Extension by the end of 2024. Separately, the PHOENIX survival data collection efforts will continue at the encouragement of ALS specialists.
Current wording
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 wording
As of June 30, 2024, we had cash, cash equivalents and short-term investments of $309.8 million. In April 2024, we announced a restructuring to focus our financial resources on upcoming clinical milestones. Under the restructuring, we started the process to reduce 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 short-term investments as of June 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 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.
Previous wording
We expect to finance our near-term operations through our existing cash, cash equivalents and short-term investments and if needed, the sale of equity, debt financings or other capital sources, including potential collaborations with other companies, royalty financings, or other strategic transactions. Our inability to raise capital or secure other funding as and when needed could have a negative impact on our financial condition and ability to pursue our business strategies. There can be no assurances that our current operating plan will be achieved or that additional funding, if required, will be available on terms acceptable to us, or at all.
Current wording
We expect to finance our near-term operations through our existing cash, cash equivalents and marketable securities and 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
Product revenue, net recognized during the three and six months ended June 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.
Current wording
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.
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 includes 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, 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.
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.
Current 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.
Previous wording
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™and remove the product from the market in the U.S. and Canada based on topline results from the Phase 3 PHOENIX trial. As a result, we did not generate significant revenue from product sales for the three months ended June 30, 2024 and the balance primarily represents GTN adjustments reflecting actual rebate and return activity during the period. For the three months ended June 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 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.
Previous wording
Research and development expenses were $23.3 million for the three months ended June 30, 2024, compared to $29.0 million for the three months ended June 30, 2023. During these periods, most of our research and development expenses were related to the development and clinical trials of AMX0035. The decrease was primarily due to a $6.9 million decrease in spending on AMX0035 for the treatment of ALS due to the completion of the Phase 3 PHOENIX trial, which failed to meet its prespecified primary and secondary endpoints, and a $2.5 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 $1.9 million increase in spending on AMX0035 for the treatment of PSP and a $1.8 million increase in other costs. The increase in spending on
Current wording
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.
Previous wording
Selling, general and administrative expenses were $21.6 million for the three months ended June 30, 2024 compared to $43.4 million for the three months ended June 30, 2023. The decrease was primarily due to a decrease of $12.1 million in payroll and personnel-related costs, a decrease of $6.7 million in consulting and professional services and a decrease of $3.0 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 removing RELYVRIO®/ALBRIOZA™ from the market in the U.S. and Canada based on topline results from the global Phase 3 PHOENIX trial. The decrease in other expenses is primarily due decrease in activity to wind down commercial operations.
Current 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.
Previous wording
We recorded an income tax provision of zero and $1.9 million for the three months ended June 30, 2024 and 2023, respectively. The absence of an income tax provision for the three months ended June 30, 2024 was driven by the estimated effective tax rate for the year. The income tax benefit for the three months ended June 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.
Current wording
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.
Previous wording
Product revenue, net was $87.6 million for the six months ended June 30, 2024, compared to $169.6 million for the six months ended June 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. 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™ and remove the product from the market in the U.S. and Canada based on topline results from the Phase 3 PHOENIX trial. As a result, we did not generate significant revenue from product sales in the second quarter of 2024.
Current wording
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.
Previous wording
Cost of sales were $123.8 million for the six months ended June 30, 2024, compared to $10.9 million for the six months ended June 30, 2023. During these periods, cost of sales consisted of costs to procure, manufacture and distribute our marketed products, RELYVRIO and ALBRIOZA. 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™ and remove the product from the market in the U.S. and Canada based on topline results from the Phase 3 PHOENIX trial. As a result, the Company recorded approximately $117.9 million of charges associated with the write-down of inventory and losses on firm purchase commitments for the six months ended June 30, 2024.
Current 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.
Previous wording
The following table summarizes our research and development expenses for the six months ended June 30, 2024 and 2023 (in thousands):
Current wording
The following table summarizes our research and development expenses for the nine months ended September 30, 2024 and 2023 (in thousands):
Previous wording
Research and development expenses were $60.0 million for the six months ended June 30, 2024, compared to $53.2 million for the six months ended June 30, 2023. During these periods, most of our research and development expenses were related to the development and clinical trials of AMX0035. The increase was primarily due to a $6.1 million increase in spending on AMX0035 for the treatment of PSP, a $3.5 million increase in payroll and personnel-related costs and a $4.0 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. The increase in payroll and personnel-related costs was primarily due to an increase in the number of employees supporting research and development efforts and the increase in other costs were primarily due to an increase in preclinical development activities. This increase was offset by a $6.8 million decrease in spending on AMX0035 for the treatment of ALS due to the completion of the Phase 3 PHOENIX trial, which failed to meet its prespecified primary and secondary endpoints.
Current 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.
Previous wording
Selling, general and administrative expenses were $79.4 million for the six months ended June 30, 2024 compared to $87.4 million for the six months ended June 30, 2023. The decrease was primarily due to a decrease of $8.6 million in payroll and personnel-related costs and a decrease of $4.2 million in consulting and professional services, offset by an increase of $4.8 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 removing RELYVRIO®/ALBRIOZA™ from the market in the U.S. and Canada based on topline results from the global Phase 3 PHOENIX trial. The increase in other expenses is primarily due to an increase in spending for operations as a public company and other expenses.
Current wording
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 wording
During the three months ended June 30, 2024, restructuring expenses were approximately $22.9 million which includes employee severance and termination benefits of approximately $21.8 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.
Current wording
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.
Previous wording
We recorded an income tax provision of $0.2 million and an income tax benefit of $1.8 million for the six months ended June 30, 2024 and 2023, respectively. The income tax provision for the six months ended June 30, 2024 was driven by discrete income tax expense of $0.2 million. The income tax benefit for the six months ended June 30, 2023 was primarily driven by the estimated effective tax rate for the year, as well as discrete income tax benefit of $0.3 million.
Current wording
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.
Previous wording
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 that we had started a process with the FDA and Health Canada to voluntarily discontinue the marketing authorizations for RELYVRIO®/ALBRIOZA™ for the treatment of ALS and remove the product from the market in the U.S. and Canada. As of April 4, 2024, RELYVRIO/ALBRIOZA was no longer available for new patients. We also announced the Restructuring Plan designed to focus our resources on key clinical and preclinical programs. The Restructuring Plan includes a reduction in force which is expected to reduce our workforce by approximately 70% and a decrease in external financial commitments outside of our priority areas. We substantially completed the Restructuring Plan in the second 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 June 30, 2024, we had cash, cash equivalents and short-term investments of $309.8 million.
Current wording
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.
Previous wording
Based on our current operational plans and assumptions, we believe that our existing cash, cash equivalents, and short-term investments, 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.
Current wording
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.
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. Because we no longer qualify as an emerging growth company as defined in the JOBS Act and we are currently considered an accelerated filer, we are no longer currently entitled to rely on exemptions from certain compliance requirements that are applicable to companies that are emerging growth companies including, among other requirements, the auditor attestation requirements of Section 404(b) and reduced reporting requirements. We expect to incur significant expenses as we:
Current 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:
Previous wording
hire and retain additional personnel, such as preclinical, clinical, quality assurance, regulatory affairs, manufacturing, distribution, legal, compliance, finance, general and administrative, commercial and scientific personnel;
Current wording
hire and retain additional personnel, such as preclinical, clinical, quality assurance, regulatory affairs, manufacturing, distribution, legal, compliance, finance, general and administrative, commercial and scientific personnel; and
Previous wording
During the six months ended June 30, 2024, operating activities used $67.1 million of cash, primarily resulting from our net loss of $191.5 million, $5.8 million net accretion of discounts on investments and $8.5 million of net cash used by changes in our operating assets and liabilities, offset by $117.9 million of inventory impairment and loss on firm purchase commitments and $19.5 million of non-cash stock-based compensation expense.
Current 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.
Previous wording
Net cash used by changes in our operating assets and liabilities primarily consisted of a $36.0 million decrease in accounts receivable, net, offset by a $9.3 million increase in inventory capitalized during the period, net of inventory written-off, a decrease of $20.3 million in accrued expenses and a $17.1 million decrease in accounts payable.
Current 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.
Previous wording
During the six months ended June 30, 2023, operating activities provided $3.5 million of cash, primarily resulting from our net income of $23.6 million and $17.5 million of non-cash stock-based compensation expense, offset by $4.9 million net accretion of discounts on investments and $33.2 million of net cash used by changes in our operating assets and liabilities.
Current 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.
Previous wording
Net cash used in our operating assets and liabilities primarily consisted of a $32.6 million increase in inventory capitalized during the period and a $18.2 million increase in accounts receivable, net, offset by a $18.5 million increase in accounts payable.
Current 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.
Previous wording
During the six months ended June 30, 2024, net cash used by investing activities was $28.1 million, resulting primarily from $232.0 million of purchases of short-term investments during the period, offset by $204.0 million of investments that matured.
Current 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.
Previous wording
During the six months ended June 30, 2023, net cash provided by investing activities was $179.2 million, resulting primarily from $189.5 million of investments that matured, partially offset by $9.8 million of purchases of short-term investments during the period.
Current 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.
Previous wording
During the six months ended June 30, 2024, net cash provided by financing activities was $0.2 million. This amount consisted primarily of $0.2 million of proceeds from exercises of stock options and vesting of stock awards, net of withholding taxes paid on stock-based awards.
Current 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.
Previous wording
During the six months ended June 30, 2023, net cash provided by financing activities was $2.4 million. This amount consisted primarily of $2.6 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 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.
Previous wording
We enter into agreements in the normal course of business with CMOs for raw material purchases and manufacturing services. As disclosed in Note 18 Commitments and Contingencies on our Annual Report on Form 10-K, as of December 31, 2023, we had committed approximately $195.0 million under these agreements related to raw material purchases and manufacturing services, which were expected to be paid through 2028. While these commitments are estimates and are subject to changes based on the outcomes of ongoing negotiations with the contract manufacturing organizations, as of June 30, 2024, we estimated approximately $31.7 million of obligations under these agreements, which are expected to be paid through 2025. The actual obligations may differ from these estimates, and such differences will be reflected in our financial statements in future periods as they become known.
Current wording
We enter into agreements in the normal course of business with contract manufacturing organizations for raw material purchases and manufacturing services. As of September 30, 2024, we had approximately $27.2 million of remaining obligations under these agreements, which are expected to be paid through 2025.
Rearranged current paragraphs (1)
Current report — wording carried from elsewhere
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.
Rearranged previous paragraphs (3)
Previous report — wording carried elsewhere
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.
Previous report — wording carried elsewhere
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.
Previous report — wording carried elsewhere
During the six months ended June 30, 2024, restructuring expenses were approximately $22.9 million which includes employee severance and termination benefits of approximately $21.8 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.