CAPN2

CAMBRIDGE, Mass.--( BUSINESS WIRE )-- Amylyx Pharmaceuticals, Inc. (Nasdaq: AMLX) (“Amylyx” or the “Company”) today reported financial results for the second quarter ended June 30, 2024. “We recently expanded our late-stage pipeline with our acquisition of avexitide and now have three assets targeting orphan indications. Avexitide is Phase 3-ready with FDA Breakthrough Therapy Designation in post-bariatric hypoglycemia (PBH) and congenital hyperinsulinism, highly statistically significant data from two Phase 2 studies, and an FDA-agreed upon primary outcome for the pivotal study in PBH,” said Joshua Cohen, Co-CEO of Amylyx. “PBH represents a major unmet need with an estimated 160,000 individuals in the U.S. impacted by symptomatic PBH, which can cause brain glucose starvation, known as neuroglycopenia. We are focused on progressing avexitide into Phase 3 development, which is on track to occur in Q1 2025, with topline data anticipated in 2026.” “Our recent restructuring and our focus on efficient and targeted clinical development is expected to help advance all four programs efficiently to potentially bring new treatments to communities with high unmet needs. We continue to make important progress in neurodegenerative diseases and are excited to share updated data from our Wolfram syndrome program in the months ahead,” added Justin Klee, Co-CEO of Amylyx. “We also look forward to initiating a multiple ascending dose clinical trial of AMX0114 in ALS before the end of the year and reporting interim data from our AMX0035 progressive supranuclear palsy program in mid-2025.” Second Quarter and Recent Corporate Updates: Acquired avexitide, a Phase 3-ready GLP-1 receptor antagonist with U.S. Food and Drug Administration (FDA) Breakthrough Therapy Designation and Orphan Drug Designation in hyperinsulinemic hypoglycemia. Avexitide has been evaluated in five clinical trials for post-bariatric hypoglycemia (PBH) and has also been studied in three clinical trials for congenital hyperinsulinism (HI), two indications characterized by hyperinsulinemic hypoglycemia. In previous Phase 2 and Phase 2b studies in PBH, avexitide showed statistically significant reductions in hypoglycemic events. FDA guidance for industry combined with initial FDA feedback specific to the pivotal Phase 3 program of avexitide for PBH suggest that reduction in hypoglycemic events could be an endpoint to support approval following positive results from a pivotal Phase 3 clinical trial. Announced interim data from the ongoing Phase 2 HELIOS clinical trial of AMX0035 (sodium phenylbutyrate [PB] and taurursodiol [TURSO, also known as ursodoxicoltaurine]) in eight adults living with Wolfram syndrome which demonstrated encouraging improvement in glycemic control, pancreatic beta cell function, and vision. Wolfram syndrome is a prototypical disease of endoplasmic reticulum stress that is rare, progressive, and monogenic and is characterized by childhood-onset diabetes mellitus, optic nerve atrophy, deafness, diabetes insipidus, and neurodegeneration. In April, the Company hosted a virtual webcast to discuss these data with Dr. Fumihiko Urano, a leading expert in Wolfram syndrome, the Principal Investigator of the Phase 2 HELIOS clinical trial in Wolfram syndrome, and the Samuel E. Schechter Professor of Medicine in the Division of Endocrinology, Metabolism & Lipid Research at Washington University School of Medicine in St. Louis. A replay is available here . Received Orphan Drug Designation from the European Commission (EC) for AMX0035 for the treatment of Wolfram syndrome. The designation was based on a positive opinion issued by the Committee for Orphan Medicinal Products (COMP) of the European Medicines Agency (EMA). The FDA previously granted AMX0035 Orphan Drug Designation for the treatment of Wolfram syndrome in 2020. Upcoming Expected Milestones: The Company plans to initiate a multiple ascending dose clinical trial of AMX0114 in people living with ALS in the second half of 2024 . Amylyx has completed IND-enabling studies of AMX0114, a potent antisense oligonucleotide targeting inhibition of calpain-2, a well-established target in a number of neurological diseases and a protease known to cleave many substrates including neurofilament, tau, and TDP43 proteins. Amylyx has observed rescue of cellular degeneration and neurofilament biology in multiple cellular experiments with AMX0114. Amylyx plans to present updated Phase 2 HELIOS topline data at the International Society for Pediatric and Adolescent Diabetes (ISPAD) Conference in Lisbon, Portugal, October 16-19, 2024, including data for all 12 participants at Week 24 and additional longer-term data for any participant that completed their Week 36 or 48 visit prior to the data cutoff. The Company is engaging with stakeholders, including the FDA, and planning for a single Phase 3 clinical trial. Amylyx will share additional details on the clinical trial design once finalized. Amylyx expects to initiate its Phase 3 program for avexitide in PBH in Q1 2025. Topline data are anticipated in 2026. Data from an interim analysis of the ORION study of AMX0035 in progressive supranuclear palsy (PSP) continue to be expected in mid-2025. The Company introduced an operationally seamless Phase 2b/3 study design into ORION. The first part will include approximately 100 people living with PSP. Amylyx plans to conduct an interim analysis in these participants and evaluate topline outcomes through Week 24. PSP is considered a tauopathy based on the strong genetic linkage of tau variants to the disease and presence of tau pathology in post-mortem brain samples. AMX0035 has been shown to significantly reduce tau in cerebrospinal fluid (CSF) in a Phase 2, randomized, placebo-controlled trial in Alzheimer’s disease. Financial Results for the Second Quarter Ended June 30, 2024 Net product revenue: Net product revenue was $(1.0) million for the three months ended June 30, 2024, as a result of adjustments to gross-to-net revenue reserve estimates. This is compared to net product revenue of $98.2 million for the same period in 2023. On April 4, 2024, the Company announced that it had started a process with the FDA and Health Canada to voluntarily discontinue the marketing authorizations for RELYVRIO ® and ALBRIOZA™ and remove the product from the market based on topline results from the global Phase 3 PHOENIX trial, which failed to meet its prespecified primary and secondary endpoints. For the three months ended June 30, 2023, net product revenue was primarily related to units of RELYVRIO and ALBRIOZA sold in the U.S. and Canada. Cost of Sales: Cost of sales were $7.4 million in the three months ended June 30, 2024, compared to cost of sales of $5.6 million for the same period in 2023. Cost of sales in the three months ended June 30, 2024 primarily relate to losses on firm purchase commitments under Amylyx’ commercial manufacturing supply agreements for AMX0035 that were established prior to the results from the Phase 3 PHOENIX trial. R&D Expenses: Research and development expenses were $23.3 million for the three months ended June 30, 2024, compared to $29.0 million for the same period in 2023. The decrease was primarily due to a decrease in payroll and personnel-related costs and a decrease in clinical 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 announced on April 4, 2024. The decrease in clinical expenses is primarily due to a decrease in spending on AMX0035 for the treatment of ALS due to the completion of the Phase 3 PHOENIX trial. SG&A Expenses: Selling, general and administrative expenses were $21.6 million for the three months ended June 30, 2024, compared to $43.4 million for the same period in 2023. The decrease was primarily due to a decrease in payroll and personnel-related costs and a decrease in consulting and professional services. 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 announced on April 4, 2024. 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 Phase 3 PHOENIX trial. Restructuring Expenses: Restructuring expenses were $22.9 million for the three months ended June 30, 2024, compared to zero for the same period in 2023. Restructuring expenses included employee severance and termination benefits of approximately $21.8 million, contract termination costs, impairment of long-lived assets and other costs. The Company substantially completed its restructuring plan during the second quarter of 2024. Net Loss: Net loss for the three months ended June 30, 2024 was $72.7 million, or $1.07 per share, compared to net income of $22.1 million, or $0.31 per diluted share for the same period in 2023. Cash Position: Cash, cash equivalents, and short-term investments were $309.8 million at June 30, 2024, compared to $373.3 million at March 31, 2024. The Company expects cash runway into 2026. Investor Conference Call Information Amylyx’ management team will host a conference call and webcast today, August 8, 2024, at 8:00 a.m. ET to discuss financial results and provide an update on the business. To access the conference call, please dial +1 (800)-836-8184 (U.S. & Canada) or +1 (646)-357-8785 (international) at least 10 minutes prior to the start time and ask to be joined into the Amylyx Pharmaceuticals call. A live audio webcast of the call will be available under “Events and Presentations” in the Investor section of the Company’s website, https://investors.amylyx.com/news-events/events . The webcast will be archived and available for replay for 90 days following the event. Available Information We periodically provide other information for investors on our corporate website, https://amylyx.com , and our investor relations website, https://investors.amylyx.com . This includes press releases and other information about financial performance, information on corporate governance, and details related to our annual meeting of stockholders. We intend to use our website as a means of disclosing material non-public information and for complying with our disclosure obligations under Regulation FD. Accordingly, investors should monitor our website, in addition to following the Company’s press releases, SEC filings, and public conference calls and webcasts. About Avexitide Avexitide is an investigational, first-in-class glucagon-like peptide-1 (GLP-1) receptor antagonist with the potential to treat hyperinsulinemic hypoglycemia that has been evaluated in five Phase 2 clinical studies for post-bariatric hypoglycemia (PBH) and has also been studied in congenital hyperinsulinism (HI). The U.S. Food and Drug Administration (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 excessive GLP-1 to mitigate hypoglycemia by decreasing insulin secretion and stabilizing glucose levels. In PBH, excessive GLP-1 can lead to the hypersecretion of insulin and subsequent serious hypoglycemic events. In two Phase 2 PBH trials, avexitide demonstrated highly statistically significant reductions in hypoglycemic events. These events can lead to autonomic and neuroglycopenic symptoms that can have a devastating impact on daily living. About AMX0035 AMX0035 is an investigational, oral, fixed-dose combination of sodium phenylbutyrate (PB) and taurursodiol (TURSO; also known as ursodoxicoltaurine outside of the U.S.). AMX0035 is designed to slow or mitigate neurodegeneration by targeting endoplasmic reticulum (ER) stress and mitochondrial dysfunction, two connected central pathways that lead to cell death and neurodegeneration. Preclinical studies have provided evidence that AMX0035 may reduce cell death and improve cellular function, also supporting the synergistic effect of AMX0035 compared to individual compounds. AMX0035 is being studied as a potential treatment in neurodegenerative diseases, including Wolfram syndrome and progressive supranuclear palsy (PSP). About AMX0114 AMX0114 is an investigational, antisense oligonucleotide designed to target the gene encoding calpain-2, a key contributor to the axonal (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 has been implicated in the pathogenesis of ALS based on findings of elevated levels of calpain-2 and its cleavage products in postmortem ALS tissue, therapeutic benefit of calpain-2 modulation in animal models of ALS, and the role of calpain-2 in cleaving neurofilament, a broadly researched biomarker in ALS. Preclinical studies completed to date have shown that AMX0114 achieves 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. About Post-Bariatric Hypoglycemia (PBH) Symptomatic post-bariatric hypoglycemia (PBH) is a condition that affects approximately 8% of people who have undergone bariatric surgery. It is characterized by exaggerated secretion of glucagon-like peptide-1 (GLP-1), dysregulated secretion of insulin, and a rapid drop in blood sugar. PBH can cause serious hypoglycemic events associated with brain glucose starvation, known as neuroglycopenia, including impaired cognition, cardiac arrhythmias, loss of consciousness, and seizures. PBH is associated with a high degree of disability and can result in major disruptions to life, including falls, motor vehicle accidents, and job and income loss. It is estimated that ~160,000 people are currently living with symptomatic PBH in the U.S., classifying it as an orphan condition. About Congenital Hyperinsulinism (HI) Congenital hyperinsulinism (HI) is a rare disease characterized by hypersecretion of insulin leading to severe, persistent hypoglycemia in infants and young children with limited therapeutic options. Common symptoms of congenital HI include lack of energy, irritability, lethargy, and excessive hunger. Repeated episodes of low blood glucose increase the risk for serious complications such as breathing difficulties, seizures, intellectual disability, vision loss, brain damage, and coma. About the HELIOS Trial The HELIOS trial ( NCT05676034 ) is a 12-participant, open-label 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. About Wolfram Syndrome Wolfram syndrome is a rare, progressive, monogenic disease characterized by childhood-onset diabetes, optic nerve atrophy, and neurodegeneration. Common manifestations of Wolfram syndrome include diabetes mellitus, optic nerve atrophy, central diabetes insipidus, sensorineural deafness, neurogenic bladder, and progressive neurologic difficulties. The prognosis of Wolfram syndrome is poor, and many people with the disease die prematurely with severe neurological disabilities. Literature suggests approximately 3,000 people are living with Wolfram syndrome in the U.S. Wolfram syndrome is often characterized as a prototypical disease of endoplasmic reticulum (ER) stress. ER stress and mitochondrial dysfunction are believed to drive the underlying disease pathophysiology in Wolfram syndrome. Individuals with Wolfram syndrome generally have mutations in the WFS1 gene, which encodes wolframin, a protein spanning the membrane of the ER. Wolframin is thought to play a role in protein folding and aid in the maintenance of ER function by regulating calcium levels. Loss of wolframin function leads to ER stress and impaired mitochondrial dynamics. About the ORION Trial The ORION trial ( NCT06122662 ) is a global, randomized, double-blind, placebo-controlled Phase 2b/3 clinical trial designed to assess the efficacy, safety, and tolerability of AMX0035 compared to placebo in people living with progressive supranuclear palsy (PSP). ORION was designed and planned in collaboration with key global academic leaders, people living with PSP and their caregivers, and industry advocacy organizations. About PSP Progressive supranuclear palsy (PSP) is a sporadic, rare, and adult-onset neurodegenerative disorder that affects walking and balance, eye movement, swallowing, and speech. People living with PSP have a life expectancy of six to eight years after initial diagnosis, and its epidemiology is similar to that of amyotrophic lateral sclerosis (ALS). PSP typically begins in late-middle age and rapidly progresses over time. The disease affects approximately seven in 100,000 people worldwide, and there are currently no disease-modifying therapies approved for the treatment of PSP. PSP is characterized by abnormal tau inclusions and is consequently also known as a tauopathy. Similar to other neurodegenerative diseases, pathophysiologic changes underlying PSP are multifactorial, with several genetic and environmental factors likely contributing to tau dysfunction and aggregation. Multiple pathways, including genetic mutations, endoplasmic reticulum (ER) stress, and the activation of unfolded protein response, mitochondrial dysfunction, and neuroinflammation have been implicated as contributors to tau dysfunction and aggregation. About ALS Amyotrophic lateral sclerosis (ALS, also known as motor neuron disease) 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. More than 90% of people with ALS have sporadic disease, showing no clear family history. ALS affects around 30,000 people in the U.S., and more than 30,000 people are estimated to be living with ALS in Europe (European Union and the United Kingdom). People living with ALS have a median survival of approximately two years from diagnosis. About Amylyx Pharmaceuticals Amylyx 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. The Company has preclinical or clinical development programs underway in neurodegenerative, neuroendocrine, and endocrine diseases. Since its founding, Amylyx has been guided by science to address unanswered questions, keeping communities at the heart and center of all decisions. Amylyx is headquartered in Cambridge, Massachusetts. For more information, visit amylyx.com and follow us on LinkedIn and X . For investors, please visit investors.amylyx.com . Forward-Looking Statements Statements contained in this press release and related comments in our earnings conference call regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, the potential of AMX0035 (sodium phenylbutyrate and taurursodiol) as a treatment for Wolfram syndrome and PSP or other neurodegenerative diseases; expectations regarding the timing of the announcement of results from the Company’s Phase 3 ORION trial of AMX0035 for the treatment of PSP, and additional results from the Company’s Phase 2 HELIOS trial of AMX0035 for the treatment of Wolfram syndrome and plans to possibly initiate a phase 3 trial, including planned discussions with regulatory authorities related thereto; the potential for AMX0114 as a treatment for ALS and the planned initiation of a trial evaluating AMX0114 in ALS; expectations regarding the Company’s ability to develop, manufacture and commercialize avexitide, if approved; the potential for avexitide as a treatment for PBH; expectations regarding the timing for initiation and readout of the Phase 3 avexitide program in PBH; and expectations regarding the Company’s cash runway and longer-term strategy. Any forward-looking statements in this press release and related comments in the Company's earnings conference call are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. Risks that contribute to the uncertain nature of the forward-looking statements include: the success, cost, and timing of Amylyx’ program development activities; Amylyx’ ability to execute on its regulatory development plans and expectations regarding the timing of results from its planned data announcements and initiation of clinical studies; the risk that early-stage results may not reflect later-stage results; Amylyx’ ability to fund operations, and the impact that global macroeconomic uncertainty, geopolitical instability, and public health events will have on Amylyx’ operations, as well as the risks and uncertainties set forth in Amylyx’ United States Securities and Exchange Commission (SEC) filings, including Amylyx’ Annual Report on Form 10-K for the year ended December 31, 2023, and subsequent filings with the SEC. All forward-looking statements contained in this press release and related comments in our earnings conference call speak only as of the date on which they were made. Amylyx undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law. AMYLYX PHARMACEUTICALS, INC. CONDENSED CONSOLIDATED BALANCE SHEETS UNAUDITED (in thousands) June 30, 2024 December 31, 2023 Assets Cash, cash equivalents and short-term investments $ 309,812 $ 371,362 Accounts receivable, net 4,091 40,050 Inventories — 83,280 Prepaid expenses and other current assets 12,819 14,931 Other assets 5,440 7,831 Total assets $ 332,162 $ 517,454 Liabilities and Stockholders’ Equity Accounts payable and accrued expenses $ 67,712 $ 79,785 Other liabilities 3,141 4,237 Total liabilities 70,853 84,022 Stockholders’ equity 261,309 433,432 Total liabilities and stockholders' equity $ 332,162 $ 517,454 AMYLYX PHARMACEUTICALS, INC. CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS UNAUDITED (in thousands, except share and per share data) Three Months Ended June 30, Six Months Ended June 30, 2024 2023 2024 2023 Product revenue, net $ (1,023 ) $ 98,216 $ 87,620 $ 169,644 Operating expenses: Cost of sales 8 5,580 5,953 10,863 Cost of sales - inventory impairment and loss on firm purchase commitments 7,410 — 117,871 — Research and development 23,347 29,044 59,955 53,236 Selling, general and administrative 21,647 43,391 79,406 87,397 Restructuring expenses 22,851 — 22,851 — Total operating expenses 75,263 78,015 286,036 151,496 (Loss) income from operations (76,286 ) 20,201 (198,416 ) 18,148 Other income, net 3,586 3,806 7,165 7,262 (Loss) income before income taxes (72,700 ) 24,007 (191,251 ) 25,410 Provision for income taxes — 1,933 242 1,763 Net (loss) income $ (72,700 ) $ 22,074 $ (191,493 ) $ 23,647 Net (loss) income per share Basic $ (1.07 ) $ 0.33 $ (2.82 ) $ 0.35 Diluted $ (1.07 ) $ 0.31 $ (2.82 ) $ 0.34 Weighted-average shares used in computing net (loss) income per share Basic 68,024,929 67,233,617 67,939,642 66,976,871 Diluted 68,024,929 70,132,040 67,939,642 70,471,821

- Avexitide is a novel, first-in-class GLP-1 receptor antagonist with the potential to treat hyperinsulinemic hypoglycemia - FDA Breakthrough Therapy Designation granted for avexitide for post-bariatric hypoglycemia (PBH) and congenital hyperinsulinism - Acquisition builds on Amylyx’ endocrine and neuroscience expertise and aligns with pipeline focus of delivering important potential treatment options to communities with high unmet needs - Phase 3 program for avexitide in PBH expected to begin in Q1 2025, with data readout anticipated in 2026; FDA has agreed to the primary endpoint expected to be utilized in Phase 3 - Data from two Phase 2 studies of avexitide in people with PBH demonstrated highly statistically significant reductions in severe hypoglycemic events, an endpoint supported by the FDA - Avexitide was generally well tolerated, with a favorable safety pro across five clinical trials in people with PBH - Management to host conference call and webcast today at 8:00 a.m. Eastern Time CAMBRIDGE, Mass.--(BUSINESS WIRE)--Amylyx Pharmaceuticals, Inc. (NASDAQ: AMLX) (“Amylyx” or the “Company”) today announced the acquisition of avexitide from Eiger BioPharmaceuticals, Inc. (“Eiger”). Avexitide has been studied for the potential treatment of hyperinsulinemic hypoglycemia to date. “Since Amylyx was founded, we have been guided by a rigorous approach to our science to bring potential treatments to communities with high unmet needs. When we reviewed all the compelling data supporting avexitide, it clearly aligned with our strategic scientific criteria, expertise, and community values, and we are excited to build upon the important work done to date to study this asset,” said Joshua Cohen and Justin Klee, Co-CEOs of Amylyx. Avexitide is an investigational, first-in-class glucagon-like peptide-1 (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 (HI), two indications characterized by hyperinsulinemic hypoglycemia. The U.S. Food and Drug Administration (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, excessive GLP-1 can lead to the hypersecretion of insulin and subsequent severe hypoglycemic events, including autonomic and neuroglycopenic symptoms if left unaddressed. 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 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. Amylyx expects to begin the Phase 3 program for avexitide in PBH in Q1 2025. Furthermore, Amylyx is actively engaging in discussions with the broader congenital HI community, including experts in the field, to develop a path forward based on promising Phase 2 study results conducted at Children's Hospital of Philadelphia. Avexitide will be added to Amylyx’ current pipeline programs that have been in research and development for several years: AMX0035 for the treatment of Wolfram syndrome, AMX0035 for the treatment of progressive supranuclear palsy, and AMX0114, the Company’s antisense oligonucleotide targeting calpain-2 for the treatment of amyotrophic lateral sclerosis, or ALS. Avexitide in PBH: Key Clinical Trial Results to Date The following table shows key results from the Phase 2, randomized, placebo-controlled crossover study (PREVENT) that evaluated efficacy and safety of avexitide for treatment of PBH following Roux-en-Y gastric bypass surgery. The results showed that, compared with placebo, avexitide 30 mg twice daily (BID) and 60 mg once daily (QD) significantly increased mean plasma glucose nadir (prespecified primary endpoint) and lowered insulin peak, corresponding to 50% and 75% fewer participants requiring rescue during mixed meal tolerance testing, respectively. Significant reductions in rates of Levels 1, 2, and 3 hypoglycemia were observed. Continuous glucose monitoring (CGM) demonstrated reductions in time in hypoglycemia without induction of clinically relevant hyperglycemia. Outcomea N=17 Avexitide 30 mg BID Avexitide 60 mg QD Improvement vs. Placebo p-value Improvement vs. Placebo p-value Post Prandial Glucose Nadir (Primary Endpoint) 21% higher 0.001 26% higher 0.0002 Peak Insulin Level (Secondary Endpoint) 23% lower 0.029 21% lower 0.042 Rate of Level 1 Hypoglycemia 30% lower 0.072 61% lower 0.001 Rate of Level 2 Hypoglycemia 40% lower 0.040 60% lower 0.004 Rate of Level 3 (Severe) Hypoglycemia 23% lower 0.22 56% lower 0.014 aLevel 1 hypoglycemia: self-monitoring of blood glucose (SMBG) <70 mg/dL; Level 2 hypoglycemia: SMBG <54 mg/dL; Level 3 hypoglycemia: a severe event characterized by altered mental and/or physical functioning that requires assistance from another person for recovery. Avexitide was generally well tolerated. The most common adverse events were injection site bruising, headache, and nausea; these occurred more often with placebo than either avexitide dose. No participants withdrew due to adverse events. A Phase 2b open-label, investigator-initiated, cross-over study of higher dose avexitide (45 mg BID and 90 mg QD) was completed in a broader eligible population of 16 participants with PBH following Roux-en-Y gastric bypass surgery, vertical sleeve gastrectomy, esophagectomy, Nissen fundoplication, or gastrectomy. This trial met both its primary endpoint of number of diurnal Level 2 hypoglycemia events (glucose <54mg/dL) as measured by CGM as well as its secondary endpoints, which includes the rate of Level 2 hypoglycemia, rate of Level 3 hypoglycemia, percent diurnal time <70 mg/dL as measured by CGM, and percent diurnal time <54 mg/dL as measured by CGM. Avexitide was successful in reducing the frequency of hypoglycemia up to 65% and the amount of time in hypoglycemia up to 64%. The below table shows results of avexitide at both doses of 45 mg BID and 90 mg QD compared to medical nutrition therapy alone. Outcome N=16 Avexitide 45 mg BID Avexitide 90 mg QD Decrease from Baseline p-value Decrease from Baseline p-value Rate of Level 1 Hypoglycemia 54% lower 0.003 68% lower 0.0005 Rate of Level 2 Hypoglycemia (Secondary Endpoint)a 57% lower 0.003 53% lower 0.004 Rate of Level 3 (Severe) Hypoglycemia (Secondary Endpoint)b 68% lower 0.0003 66% lower 0.0003 aRate of Level 2 hypoglycemia: self-monitoring of blood glucose (SMBG) <54 mg/dL. bRate of Level 3 hypoglycemia: severe event characterized by altered mental and/or physical function requiring assistance. There were no reported serious adverse events, and adverse events were mostly mild to moderate and resolved without medical treatment. The most common adverse events included diarrhea, headache, bloating, and injection site reaction/bruising. No participant withdrew due to adverse events. “PBH is a debilitating condition with no approved treatment options, and we look forward to advancing this critical work with avexitide into Phase 3 for individuals with PBH based on the totality of data from five clinical trials, and informed by our ongoing work to address endocrine and metabolic aspects of Wolfram syndrome. We also are continuing our conversations with the congenital HI community regarding the clinical development of avexitide in congenital HI to develop a path forward,” said Camille L. Bedrosian, MD, Chief Medical Officer of Amylyx. “While we are excited to study this new scientific pathway in hyperinsulinemic hypoglycemia, our research in ALS and other neurodegenerative diseases continues through our AMX0035 and AMX0114 programs, guided by the understanding that people living with these devastating diseases have no time to wait – we must continue to research and collaborate with urgency.” Transaction Details On July 9, 2024, Amylyx completed the acquisition of substantially all of the rights, title and interests in, to and under those assets and interests used by the seller in the development, manufacture and commercialization of avexitide from Eiger for $35.1 million plus the aggregate amount of determined cure costs and assumed liabilities. As part of the transaction, Amylyx assumed certain contractual obligations from Eiger, including a 3% royalty on future sales of avexitide in PBH, if approved, to certain academic institutions. Investor Conference Call Information Amylyx’ management team will host a conference call and webcast today, July 10, 2024, at 8:00 a.m. ET to discuss the asset acquisition. To access the conference call, please dial +1 (800) 836-8184 (U.S. and Canada) or +1 (646) 357-8785 (international) at least 10 minutes prior to the start time and ask to be joined into the Amylyx Pharmaceuticals call. A live audio webcast of the call will be available under “Events and Presentations” in the Investor section of the Company’s website, , and will be available for replay for 90 days following the event. About Avexitide Avexitide is an investigational, first-in-class glucagon-like peptide-1 (GLP-1) receptor antagonist that has been evaluated in five Phase 2 clinical studies for post-bariatric hypoglycemia (PBH) and has also been studied in congenital hyperinsulinism (HI), with U.S. Food and Drug Administration (FDA) Breakthrough Therapy Designation for both indications and FDA Rare Pediatric Disease Designation in congenital HI. Avexitide is designed to bind to the GLP-1 receptor on pancreatic islet beta cells and block the effect of excessive GLP-1 to mitigate hypoglycemia by decreasing insulin secretion and stabilizing glucose levels. In PBH, excessive GLP-1 can lead to the hypersecretion of insulin and subsequent severe hypoglycemic events. In two Phase 2 PBH trials, avexitide demonstrated highly statistically significant reductions in hypoglycemic events. These events can lead to autonomic and neuroglycopenic symptoms that can have a devastating impact on daily living. About Post-Bariatric Hypoglycemia (PBH) Symptomatic post-bariatric hypoglycemia (PBH) is a condition that affects approximately 8% of people who have undergone bariatric surgery. It is characterized by exaggerated secretion of glucagon-like peptide-1 (GLP-1), dysregulated secretion of insulin, and a rapid drop in blood sugar. PBH can cause severe hypoglycemic events associated with brain glucose starvation, known as neuroglycopenia, including impaired cognition, cardiac arrythmias, loss of consciousness, and seizures. PBH is associated with a high degree of disability and can result in major disruptions to life, including falls, motor vehicle accidents, and job and income loss. It is estimated that ~160,000 people are currently living with symptomatic PBH in the U.S., classifying it as an orphan condition. About Congenital Hyperinsulinism (HI) Congenital hyperinsulinism (HI) is a rare disease characterized by hypersecretion of insulin leading to severe, persistent hypoglycemia in infants and young children with limited therapeutic options. Common symptoms of congenital HI include lack of energy, irritability, lethargy, and excessive hunger. Repeated episodes of low blood glucose increase the risk for serious complications such as breathing difficulties, seizures, intellectual disability, vision loss, brain damage, and coma. About AMX0035 AMX0035 is an oral, fixed-dose combination of sodium phenylbutyrate (PB) and taurursodiol (TURSO; also known as ursodoxicoltaurine outside of the U.S.). AMX0035 was designed to slow or mitigate neurodegeneration by targeting endoplasmic reticulum (ER) stress and mitochondrial dysfunction, two connected central pathways that lead to cell death and neurodegeneration. Preclinical studies have provided evidence that the proprietary combination of PB and TURSO and their complementary mechanisms of action targets cell death and better prevents neurodegeneration than targeting either mechanism of action alone. AMX0035 is being studied as a potential treatment in neurodegenerative diseases, including Wolfram syndrome and progressive supranuclear palsy (PSP). About AMX0114 AMX0114 is an antisense oligonucleotide designed to target the gene encoding calpain-2, a key contributor to the axonal (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 has been implicated in the pathogenesis of ALS based on findings of elevated levels of calpain-2 and its cleavage products in postmortem ALS tissue, therapeutic benefit of calpain-2 modulation in animal models of ALS, and the role of calpain-2 in cleaving neurofilament, a broadly researched biomarker in ALS. Preclinical studies completed to date have shown that AMX0114 achieves 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. About Amylyx Pharmaceuticals Amylyx 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. Since its founding, Amylyx has been guided by science to address unanswered questions, keeping communities at the heart and center of all decisions. Amylyx is headquartered in Cambridge, Massachusetts. For more information, visit amylyx.com and follow us on LinkedIn and X (formerly Twitter). For investors, please visit investors.amylyx.com. Forward-Looking Statements Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, Amylyx’ expectations regarding: plans for initiating a Phase 3 clinical program of avexitide, including interactions with regulatory authorities; the possibility that results from a Phase 3 program could support FDA approval of avexitide in PBH; and expectations regarding the benefits of the acquisition of avexitide. Any forward-looking statements in this press release are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. Risks that contribute to the uncertain nature of the forward-looking statements include the risks and uncertainties set forth in Amylyx’ United States Securities and Exchange Commission (SEC) filings, including Amylyx’ Annual Report on Form 10-K for the year ended December 31, 2023, and subsequent filings with the SEC. All forward-looking statements contained in this press release speak only as of the date on which they were made. Amylyx undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.

Company plans to engage with FDA based on interim data from the Phase 2 HELIOS clinical trial demonstrating improvements in pancreatic function, glycemic control, and vision in participants with Wolfram syndrome treated with AMX0035; topline data from all 12 participants at Week 24 anticipated in fall of 2024 Interim analysis from the ORION study of AMX0035 in progressive supranuclear palsy continues to be expected in mid-2025 Amylyx expects to initiate clinical trial of AMX0114 in ALS in the second half of 2024 Cash, cash equivalents and short-term investments of $373.3 million at March 31, 2024 provides expected cash runway into 2026 Management to host conference call and webcast today at 8:00 a.m. Eastern Time CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Amylyx Pharmaceuticals, Inc. (Nasdaq: AMLX) (“Amylyx” or the “Company”) today reported financial results for the first quarter ended March 31, 2024. “As an organization deeply committed to ending the suffering caused by neurodegenerative diseases, we took swift action in the first quarter of 2024 to focus our resources on key clinical and preclinical programs and build on the vital foundation we have laid to date as we drive toward our mission. We are focused on diseases where there is a high unmet need for better therapies and where there are well-defined measurable biomarkers, rigorous supporting preclinical data, and well-defined rationales for our therapy’s mechanism of action,” said Joshua Cohen and Justin Klee, Co-CEOs of Amylyx. “We anticipate multiple near-term catalysts for our pipeline, including data from our ongoing clinical trials of AMX0035 in Wolfram syndrome this fall and PSP in mid-2025. We are also excited to bring AMX0114, our potent antisense oligonucleotide targeting inhibition of calpain-2, to the clinic in ALS in the second half of 2024.” Recent Corporate Updates: Amylyx announced formal intention to remove RELYVRIO®/ALBRIOZA™ from the market based on topline results from the Phase 3 PHOENIX trial. In April, the Company announced that it started a process with the U.S. Food and Drug Administration (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. This decision was informed by topline PHOENIX trial results, engagement with regulatory authorities, and discussions with the ALS community. As of April 4, 2024, RELYVRIO/ALBRIOZA is no longer available for new patients, and patients currently on therapy in the U.S. and Canada who, in consultation with their physician, wish to stay on treatment can be transitioned to a free drug program. Amylyx also announced a restructuring to focus the Company’s financial resources on key programs and extend expected cash runway into 2026, through anticipated data readouts for AMX0035 in Wolfram syndrome and PSP, and AMX0114 in ALS. Interim data from the ongoing Phase 2 HELIOS clinical trial of AMX0035 (sodium phenylbutyrate [PB] and taurursodiol [TURSO, also known as ursodoxicoltaurine]) in eight adults living with Wolfram syndrome demonstrated encouraging improvement in pancreatic beta cell function, glycemic control, and vision. Amylyx is planning to meet with FDA based on these interim data. Wolfram is a rare, progressive, genetic disease impacting approximately 3,000 people in the U.S. There are no approved treatment options for Wolfram. The majority of people with Wolfram carry mutations in the WFS1 gene, which encodes a protein called wolframin that spans the membrane of the endoplasmic reticulum (ER). Wolfram is considered a prototypical ER stress disorder because of the clear link between WFS1 mutations and ER stress. AMX0035, which targets ER stress and associated mitochondrial dysfunction, has shown benefit in cellular models of the disease and a genetic animal model of the disease. The interim data from eight participants who have completed 24 weeks of treatment showed evidence of improvements in beta cell function and glycemic control, as measured by c-peptide and other markers of glucose metabolism, rather than the worsening typically expected with disease progression. All eight participants met prespecified responder criteria demonstrating either improvement or stabilization of disease according to both the Patient Reported Global Impression of Change (PGIC) and the Clinician Reported Global Impression of Change (CGIC) scales. The majority of participants reported some improvement in vision. AMX0035 was generally well-tolerated in all participants, and there have been no dropouts or discontinuations thus far. Amylyx anticipates reporting topline data from all 12 participants at Week 24 in the fall of 2024. The Company hosted a virtual webcast with Dr. Fumihiko Urano to discuss interim data from the Phase 2 HELIOS clinical trial of AMX0035 in people living with Wolfram syndrome. Dr. Urano is a leading expert in Wolfram syndrome, the Principal Investigator of the Phase 2 HELIOS clinical trial in Wolfram syndrome, and the Samuel E. Schechter Professor of Medicine in the Division of Endocrinology, Metabolism & Lipid Research at Washington University School of Medicine in St. Louis. A replay is available at . Data from an interim analysis of the ORION study of AMX0035 in PSP are expected in mid-2025. ORION is a randomized, double-blind, placebo-controlled Phase 3 clinical trial designed to assess the efficacy, safety, and tolerability of AMX0035 in people living with PSP. PSP is a rare neurological disorder that affects body movements, walking and balance, and eye movement and is characterized by widespread neurodegeneration associated with tau protein deposition in subcortical regions of the brain. PSP is considered a tauopathy based on the strong genetic linkage of tau variants to the disease and presence of tau pathology in post-mortem brain samples. Variants in ER stress-linked genes have also been associated with the disease. In addition to demonstrating that AMX0035 targets ER stress and mitochondrial dysfunction, AMX0035 has been shown to significantly reduce cerebrospinal fluid (CSF) tau in a Phase 2, randomized, placebo-controlled trial in Alzheimer’s disease. There are currently no approved therapies for the treatment of PSP, and the disease is reported to affect seven in 100,000 people worldwide. The Company plans to investigational new drug (IND) application, then initiate a multiple ascending dose clinical trial of AMX0114 in people living with ALS in the second half of 2024. Amylyx has completed IND-enabling studies of AMX0114, a potent antisense oligonucleotide targeting inhibition of calpain-2, a well-established target in a number of neurological diseases and a protease known to cleave many substrates including neurofilament, tau, and TDP43 proteins. Amylyx has observed rescue of cellular degeneration and neurofilament biology in multiple cellular experiments with AMX0114. Bernhardt G. Zeiher, MD, FCCP, FACP, appointed to Amylyx Board of Directors. Dr. Zeiher has spent more than 20 years in drug development at companies including Astellas Pharma, Pfizer, Eli Lilly and Company, and Merck and oversaw the approval of 15 new treatments that addressed people’s unmet needs in serious diseases with few to no treatment options. Financial Results for the First Quarter Ended March 31, 2024 Net product revenue: Net product revenue was $88.6 million for the three months ended March 31, 2024, compared to net product revenue of $71.4 million for the same period in 2023. During these periods, net product revenue was primarily related to units of RELYVRIO and ALBRIOZA sold in the U.S. and Canada, respectively. On April 4, 2024, the Company announced that it 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. Cost of Sales: Cost of sales were $116.4 million in the three months ended March 31, 2024, compared to cost of sales of $5.3 million for the same period in 2023. Cost of sales in the three months ended March 31, 2024 included non-cash charges of approximately $110.5 million associated with the write-down of inventory and loss on firm purchase commitments related to the Company’s decision to voluntarily discontinue the marketing authorizations for RELYVRIO/ALBRIOZA in the U.S. and Canada. During these periods, cost of sales consisted of costs to procure, manufacture, and distribute RELYVRIO and ALBRIOZA. R&D Expenses: Research and development expenses were $36.6 million for the three months ended March 31, 2024, compared to $24.2 million for the same period in 2023. The increase was primarily driven by an increase in personnel-related expenses due to added headcount to support research and development efforts, an increase in spending on the Phase 3 ORION study of AMX0035 in PSP, and an increase in preclinical development activities. SG&A Expenses: Selling, general and administrative expenses were $57.8 million for the three months ended March 31, 2024, compared to $44.0 million for the same period in 2023. The increase was primarily driven by higher personnel-related expenses due to added headcount to support the Company’s launch, commercialization initiatives, and operations as a public company, and other expenses. Net Loss: Net loss for the three months ended March 31, 2024 was $118.8 million, or $1.75 on a fully diluted per share basis, compared to a net income of $1.6 million, or $0.02 on a fully diluted per share basis for the same period in 2023. Cash Position: Cash, cash equivalents, and short-term investments were $373.3 million at March 31, 2024, compared to $371.4 million at December 31, 2023. The Company expects cash runway into 2026, which will allow the organization to deliver on key upcoming milestones, including anticipated data readouts from HELIOS (AMX0035 in Wolfram syndrome), ORION (AMX0035 in PSP), and its planned trial of AMX0114 in ALS. Investor Conference Call Information Amylyx’ management team will host a conference call and webcast today, May 9, 2024, at 8:00 a.m. ET to discuss financial results and provide an update on the business. To access the conference call, please dial +1 (877)-346-6112 (U.S. & Canada) or +1 (848)-280-6350 (international) at least 10 minutes prior to the start time and ask to be joined into the Amylyx Pharmaceuticals call. A live audio webcast of the call will be available under “Events and Presentations” in the Investor section of the Company’s website, . The webcast will be archived and available for replay for 90 days following the event. Available Information We periodically provide other information for investors on our corporate website, , and our investor relations website, . This includes press releases and other information about financial performance, information on corporate governance, and details related to our annual meeting of stockholders. We intend to use our website as a means of disclosing material non-public information and for complying with our disclosure obligations under Regulation FD. Accordingly, investors should monitor our website, in addition to following the Company’s press releases, SEC filings, and public conference calls and webcasts. About AMX0035 AMX0035 is an oral, fixed-dose combination of sodium phenylbutyrate (PB) and taurursodiol (TURSO; also known as ursodoxicoltaurine outside of the U.S.). AMX0035 was designed to slow or mitigate neurodegeneration by targeting endoplasmic reticulum (ER) stress and mitochondrial dysfunction, two connected central pathways that lead to cell death and neurodegeneration. Preclinical studies have provided evidence that AMX0035 may reduce cell death and improve cellular function, also supporting the synergistic effect of AMX0035 compared to individual compounds. AMX0035 is being studied as a potential treatment in neurodegenerative diseases, including Wolfram syndrome and progressive supranuclear palsy (PSP). About AMX0114 AMX0114 is an antisense oligonucleotide designed to target the gene encoding calpain-2, a key contributor to the axonal (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 has been implicated in the pathogenesis of ALS based on findings of elevated levels of calpain-2 and its cleavage products in postmortem ALS tissue, therapeutic benefit of calpain-2 modulation in animal models of ALS, and the role of calpain-2 in cleaving neurofilament, a broadly researched biomarker in ALS. Preclinical studies completed to date have shown that AMX0114 achieves 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. About the HELIOS Trial The HELIOS trial (NCT05676034) is a 12-participant, open-label 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. About Wolfram Syndrome Wolfram syndrome is an autosomal recessive neurodegenerative disease characterized by childhood-onset diabetes, optic nerve atrophy, and neurodegeneration. Common manifestations of Wolfram include diabetes mellitus, optic nerve atrophy, central diabetes insipidus, sensorineural deafness, neurogenic bladder, and progressive neurologic difficulties. Literature suggests approximately 3,000 people are living with Wolfram syndrome in the United States. Genetic and experimental evidence suggests that endoplasmic reticulum (ER) dysfunction is a critical pathogenic component of Wolfram. The prognosis of Wolfram is poor, and many people with the disease die prematurely with severe neurological disabilities. About the ORION Trial The ORION trial (NCT06122662) is a global, randomized, double-blind, placebo-controlled Phase 3 clinical trial designed to assess the efficacy, safety, and tolerability of AMX0035 compared to placebo in people living with progressive supranuclear palsy (PSP). ORION was designed and planned in collaboration with key global academic leaders, people living with PSP and their caregivers, and industry advocacy organizations. About PSP Progressive supranuclear palsy (PSP) is a sporadic, rare, and adult-onset neurodegenerative disorder that affects walking and balance, eye movement, swallowing, and speech. People living with PSP have a life expectancy of six to eight years after initial diagnosis, and its epidemiology is similar to that of amyotrophic lateral sclerosis (ALS). PSP typically begins in late-middle age and rapidly progresses over time. The disease affects approximately seven in 100,000 people worldwide, and there are currently no disease-modifying therapies approved for the treatment of PSP. PSP is characterized by abnormal tau inclusions and is consequently also known as a tauopathy. Similar to other neurodegenerative diseases, pathophysiologic changes underlying PSP are multifactorial, with several genetic and environmental factors likely contributing to tau dysfunction and aggregation. Multiple pathways, including genetic mutations, endoplasmic reticulum (ER) stress, and the activation of unfolded protein response, mitochondrial dysfunction, and neuroinflammation have been implicated as contributors to tau dysfunction and aggregation. About ALS Amyotrophic lateral sclerosis (ALS, also known as motor neuron disease) 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. More than 90% of people with ALS have sporadic disease, showing no clear family history. ALS affects around 30,000 people in the U.S., and more than 30,000 people are estimated to be living with ALS in Europe (European Union and the United Kingdom). People living with ALS have a median survival of approximately two years from diagnosis. About Amylyx Pharmaceuticals Amylyx Pharmaceuticals, Inc. is committed to supporting and creating more moments for the neurodegenerative disease community through the discovery and development of innovative new treatments. Amylyx is headquartered in Cambridge, Massachusetts. For more information, visit amylyx.com and follow us on LinkedIn and X, formerly known as Twitter. For investors, please visit investors.amylyx.com. Forward-Looking Statements Statements contained in this press release and related comments in our earnings conference call regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, the potential of AMX0035 (sodium phenylbutyrate and taurursodiol) as a treatment for Wolfram syndrome and PSP or other neurodegenerative diseases; expectations regarding the timing of the announcement of results from the Company’s Phase 3 ORION trial of AMX0035 for the treatment of PSP, and additional results from the Company’s Phase 2 HELIOS trial of AMX0035 for the treatment of Wolfram syndrome, including planned discussions with regulatory authorities related to the latter; the potential for AMX0114 as a treatment for ALS and the planned initiation of a trial evaluating AMX0114 in ALS; the availability of RELYVRIO/ALBRIOZA for patients currently taking RELYVRIO/ALBRIOZA; the timing and significance of learnings from the PHOENIX trial; the Company’s expectations regarding its financial performance; expectations regarding the contributions of the Company’s board of directors; and expectations regarding the Company’s cash runway and longer-term strategy. Any forward-looking statements in this press release and related comments in the Company's earnings conference call are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. Risks that contribute to the uncertain nature of the forward-looking statements include: the success, cost, and timing of Amylyx’ program development activities; Amylyx’ ability to execute on its regulatory development plans and expectations regarding the timing of results from its planned data announcements and initiation of clinical studies; the risk that early-stage results may not reflect later-stage results; Amylyx’ ability to fund operations, and the impact that global macroeconomic uncertainty, geopolitical instability, and public health events will have on Amylyx’ operations, as well as the risks and uncertainties set forth in Amylyx’ United States Securities and Exchange Commission (SEC) filings, including Amylyx’ Annual Report on Form 10-K for the year ended December 31, 2023, and subsequent filings with the SEC. All forward-looking statements contained in this press release and related comments in our earnings conference call speak only as of the date on which they were made. Amylyx undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made. AMYLYX PHARMACEUTICALS, INC. CONDENSED CONSOLIDATED BALANCE SHEETS UNAUDITED (in thousands) March 31, 2024 December 31, 2023 Assets Cash, cash equivalents and short-term investments $ 373,293 $ 371,362 Accounts receivable, net 20,351 40,050 Inventories — 83,280 Prepaid expenses and other current assets 16,890 14,931 Other assets 6,923 7,831 Total assets $ 417,457 $ 517,454 Liabilities and Stockholders’ Equity Accounts payable and accrued expenses $ 89,327 $ 79,785 Other liabilities 3,694 4,237 Total liabilities 93,021 84,022 Stockholders’ equity 324,436 433,432 Total liabilities and stockholders' equity $ 417,457 $ 517,454 AMYLYX PHARMACEUTICALS, INC. CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS UNAUDITED (in thousands, except share and per share data) Three Months Ended March 31, 2024 2023 Product revenue, net $ 88,643 $ 71,428 Operating expenses: Cost of sales 5,945 5,283 Cost of sales - inventory impairment and loss on firm purchase commitments 110,461 — Research and development 36,608 24,192 Selling, general and administrative 57,759 44,006 Total operating expenses 210,773 73,481 Loss from operations (122,130 ) (2,053 ) Other income, net 3,579 3,456 (Loss) income before income taxes (118,551 ) 1,403 Provision (benefit) for income taxes 242 (170 ) Net (loss) income $ (118,793 ) $ 1,573 Net (loss) income per share Basic $ (1.75 ) $ 0.02 Diluted $ (1.75 ) $ 0.02 Weighted-average shares used in computing net (loss) income per share Basic 67,854,356 66,717,271 Diluted 67,854,356 70,863,665 View source version on businesswire.com: Contacts Media Amylyx Media Team +1 (857) 799-7274 amylyxmediateam@amylyx.com Investors Lindsey Allen Amylyx Pharmaceuticals, Inc. +1 (857) 320-6244 Investors@amylyx.com Source: Amylyx Pharmaceuticals, Inc. View this news release online at: