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- PHOENIX Study Did Not Meet Prespecified Primary or Secondary Endpoints - Data From 664-Participant Study Reinforce That AMX0035 is Generally Safe and Well-Tolerated - Within the Next Eight Weeks, Amylyx Will Continue to Engage With Regulatory Authorities and the ALS Community to Share Topline Data; Amylyx Will Share Plans for RELYVRIO/ALBRIOZA in ALS Which May Include Voluntarily Withdrawing RELYVRIO/ALBRIOZA From the Market - At This Time, RELYVRIO/ALBRIOZA Will Continue to be Available for People Living With ALS; Amylyx Has Voluntarily Decided to Pause Promotion; Related Patient Support Services Will Remain in Place - Studies With AMX0035 in Wolfram Syndrome (WS) and Progressive Supranuclear Palsy (PSP) to Continue Based on Data Supporting its Potential in These Diseases - Amylyx to Host Investor Conference Call Today, March 8, at 8:00 a.m. ET CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Amylyx Pharmaceuticals, Inc. (NASDAQ: AMLX) (“Amylyx” or the “Company”) today announced topline results from PHOENIX, a global, 48-week, randomized, placebo-controlled Phase 3 clinical trial of AMX0035 (sodium phenylbutyrate and taurursodiol [also known as ursodoxicoltaurine]; RELYVRIO® in the U.S., ALBRIOZA™ in Canada) in people living with amyotrophic lateral sclerosis (ALS). PHOENIX did not meet its primary endpoint of reaching statistical significance (p=0.667) as measured by change from baseline in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) total score at Week 48, nor was there statistical significance seen in secondary endpoints. Amylyx plans to present the data from PHOENIX at an upcoming medical meeting and will publish the results in a medical journal later this year. Amylyx will continue to engage with regulatory authorities and the broader ALS community, including ALS specialists and other multidisciplinary experts, people living with ALS, and advocates, to discuss the results from PHOENIX within the next eight weeks and make informed decisions. Amylyx intends to share plans for RELYVRIO/ALBRIOZA in ALS, which may include voluntarily withdrawing RELYVRIO/ALBRIOZA from the market. At this time, RELYVRIO/ALBRIOZA and its related patient support program will continue to be available for people living with ALS. Amylyx has voluntarily decided to pause promotion of the medication during this time. “We are surprised and deeply disappointed by the PHOENIX results following the positive data from the CENTAUR trial. Our main priority at the moment is sharing the information with people living with ALS and their treating physicians; this is part of our continued commitment to them and our mission. Over the next eight weeks, our team will continue to engage with regulatory authorities and the ALS community to discuss the results from PHOENIX. We will be led in our decisions by two key principles: doing what is right for people living with ALS, informed by regulatory authorities and the ALS community, and by what the science tells us. On behalf of the entire Amylyx team, we are grateful to the ALS community and for the dedication of trial participants, investigators, and study site teams. With data collected from 664 participants in PHOENIX, we are certain there will be important learnings that will help inform future ALS research. We are steadfast in our commitment to the ALS community and our mission, including with AMX0035 where it has shown potential in neurodegenerative diseases such as Wolfram syndrome and progressive supranuclear palsy, and with AMX0114, our investigational antisense oligonucleotide targeting calpain-2, in ALS,” said Justin Klee and Joshua Cohen, Co-CEOs of Amylyx. PHOENIX Study Results: The Phase 3 PHOENIX study enrolled 664 adults living with ALS. Participants were randomized three-to-two to receive either AMX0035 or placebo, with both treatment groups receiving standard-of-care. Continuation of a stable dosing regimen of riluzole and/or edaravone was permitted. PHOENIX did not meet the primary endpoint: There was no significant difference observed between participants treated with AMX0035 and placebo in ALSFRS-R total score change from baseline at Week 48 (p=0.667). No significant difference was observed in the subset of participants who met the CENTAUR trial criteria. There were also no significant differences observed across secondary endpoints. Consistent safety and tolerability profile: AMX0035 was well-tolerated in PHOENIX. There were no new safety signals, reinforcing the favorable and manageable safety pro with AMX0035 to date. European participants who completed the 48-week randomized phase had the option to enroll in an open label extension of the trial of up to two years in duration, which remains ongoing. Science of AMX0035: AMX0035, a specially formulated oral fixed-dose combination of PB and TURSO, has been shown in numerous preclinical studies to have a robust, synergistic effect in targeting two different destructive neurodegenerative disease pathways by mitigating endoplasmic reticulum stress and the associated unfolded protein response and mitochondrial dysfunction thereby reducing neuronal cell death. Additionally, AMX0035 has been shown to also reduce markers associated with neurodegenerative diseases in clinical trials, including a reduction of tau, a key protein aggregate shared across several neurodegenerative diseases, and YKL-40, a marker of neuroinflammation. Update on Ongoing AMX0035 Studies: The global, randomized, double-blind, placebo-controlled Phase 3 ORION clinical study of AMX0035 in PSP remains ongoing. The first participant was dosed in December 2023, and the Company is planning for an interim analysis. Topline results continue to be anticipated in 2025 or 2026. Data from the ongoing 12-participant, single site, open-label Phase 2 HELIOS clinical study are demonstrating evidence of clinical activity of AMX0035 in Wolfram syndrome. This study is fully recruited, and the Company plans to present preliminary data in the second quarter of 2024. Investor Conference Call Information Amylyx’ management team will host a live conference call and webcast today, March 8, 2024, at 8:00 a.m. ET to discuss the results of the PHOENIX trial. To participate in the conference call, please dial +1 (877) 870-4263 (U.S.), +1 (855) 669-9657 (Canada), or +1 (412) 317-0790 (International) at least 10 minutes prior to the start time and ask to be joined into the Amylyx Pharmaceuticals call. All interested parties are invited to access a live broadcast of the call via a webcast, which will be available on the “Events and Presentations” page in the “Investors” section of the Company’s website at investors.amylyx.com/news-events/events. An archived webcast will be available on the Company's website approximately two hours after the conference call and will be available for replay for 90 days following the call. About the PHOENIX Trial PHOENIX was a 48-week, randomized, placebo-controlled, global Phase 3 clinical trial further evaluating the safety and efficacy of AMX0035 (sodium phenylbutyrate and taurursodiol) for the treatment of ALS. The primary efficacy outcome of the trial was change from baseline in ALS Functional Rating Scale-Revised (ALSFRS-R) total score at 48 weeks. Secondary endpoints include quality of life patient-reported outcome assessments, overall survival, and respiratory function as measured by slow vital capacity (SVC). Safety and tolerability were also assessed. European participants who completed the 48-week trial had the option to enroll in an open-label extension (OLE) phase. During this phase, all participants receive AMX0035, and continued safety and efficacy measures will be assessed. About the CENTAUR Trial CENTAUR was a multicenter Phase 2 clinical trial in 137 participants with ALS encompassing a 6-month randomized, placebo-controlled phase and an open-label long-term follow-up phase. The trial met its primary efficacy endpoint of reducing functional decline as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R). Overall, reported rates of adverse events and discontinuations were similar between AMX0035 and placebo groups during the 24-week randomized phase; however, gastrointestinal events occurred with greater frequency (≥2%) in the AMX0035 group. Detailed data from CENTAUR is published in the New England Journal of Medicine (NEJM) and Muscle & Nerve. The CENTAUR trial was funded, in part, by the ALS ACT grant and the ALS Ice Bucket Challenge, and was supported by The ALS Association, ALS Finding a Cure (a program of The Leandro P. Rizzuto Foundation), the Northeast ALS Consortium, and the Sean M. Healey & AMG Center for ALS at Mass General. 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 iPSC-derived human motor neurons, and improved survival of iPSC-derived human motor neurons harboring ALS-linked, pathogenic TDP-43 mutations. 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 United Kingdom). People living with ALS have a median survival of approximately two years from diagnosis. About HELIOS The HELIOS trial (NCT05676034) is a 12-participant, open-label proof of biology, Phase 2 trial designed to study the effect of AMX0035 on safety and tolerability, and various measures of endocrinological, neurological, and ophthalmologic function in adult participants living with Wolfram syndrome (WS). About Wolfram Syndrome Wolfram syndrome (WS) is an autosomal recessive neurodegenerative disease characterized by childhood-onset diabetes, optic nerve atrophy, and neurodegeneration. Common manifestations of WS include diabetes mellitus, optic nerve atrophy, central diabetes insipidus, sensorineural deafness, neurogenic bladder, and progressive neurologic difficulties. Genetic and experimental evidence suggest that endoplasmic reticulum (ER) dysfunction is a critical pathogenic component of WS. The prognosis of WS is poor, and many people with the disease die prematurely with severe neurological disabilities. About the ORION Trial The Phase 3 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). The ORION Phase 3 trial 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 AMX0035 / RELYVRIO® / ALBRIOZA™ AMX0035 is an oral, fixed-dose combination of sodium phenylbutyrate and taurursodiol (known as ursodoxicoltaurine outside of the U.S.). It is approved as RELYVRIO® to treat amyotrophic lateral sclerosis (ALS) in adults in the U.S. and approved with conditions as ALBRIOZA™ for the treatment of ALS in Canada. AMX0035 is being studied for the potential treatment of other neurodegenerative diseases, and Amylyx is exploring its treatment in other populations and regions. The formulation of RELYVRIO, ALBRIOZA, and AMX0035 is identical. RELYVRIO® (sodium phenylbutyrate and taurursodiol) Safety Information for United States WARNINGS AND PRECAUTIONS Risk in Patients with Enterohepatic Circulation Disorders, Pancreatic Disorders, or Intestinal Disorders RELYVRIO contains taurursodiol, which is a bile acid. In patients with disorders that interfere with bile acid circulation, there may be an increased risk for worsening diarrhea, and patients should be monitored appropriately for this adverse reaction. Pancreatic insufficiency, intestinal malabsorption, or intestinal diseases that may alter the concentration of bile acids may also lead to decreased absorption of either of the components of RELYVRIO. Because different enterohepatic circulation, pancreatic, and intestinal disorders have varying degrees of severity, consider consulting with a specialist. Patients with disorders of enterohepatic circulation (e.g., biliary infection, active cholecystitis), severe pancreatic disorders (e.g., pancreatitis), and intestinal disorders that may alter concentrations of bile acids (e.g., ileal resection, regional ileitis) were excluded from the study; therefore, there is no clinical experience in these conditions. Use in Patients Sensitive to High Sodium Intake RELYVRIO has a high salt content. Each initial daily dosage of 1 packet contains 464 mg of sodium; each maintenance dosage of 2 packets daily contains 928 mg of sodium. In patients sensitive to salt intake (e.g., those with heart failure, hypertension, or renal impairment), consider the amount of daily sodium intake in each dose of RELYVRIO and monitor appropriately. ADVERSE REACTIONS The most common adverse reactions (at least 15% and at least 5% greater than placebo) with RELYVRIO were diarrhea, abdominal pain, nausea, and upper respiratory tract infection. Gastrointestinal-related adverse reactions occurred throughout the study but were more frequent during the first 3 weeks of treatment. Please click here for RELYVRIO Full U.S. Prescribing Information. 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 and has operations in Canada, EMEA, and Japan. 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 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, Amylyx’ expectations regarding: interactions with regulatory authorities; the continued availability of RELYVRIO/ALBRIOZA for people living with ALS while such interactions are ongoing; the pausing of promotion of RELYVRIO/ALBRIOZA; pathways for continued access for patients if RELYVRIO/ALBRIOZA are withdrawn from the market; the possibility for Amylyx to voluntarily withdraw RELYVRIO/ALBRIOZA from the market; the continued evaluation of AMX0035 in other neurodegenerative diseases, including the timing for expected data readouts in the ORION and HELIOS studies; and the evidence of biological activity of AMX0035 in Wolfram syndrome. Any forward-looking statements in this press release and related comments in the Company's 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 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 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.

Topline data from vafidemstat's PORTICO Phase IIb trial in Borderline Personality Disorder (BPD) reported with promising results in secondary endpoints of overall severity and control of agitation/aggressionCompany planning to request an End-of-Phase II meeting with the FDA to discuss plans for a registrational Phase III trial in BPDContinues to enroll patients in Phase IIb EVOLUTION trial with vafidemstat in schizophreniaContinues to recruit patients in FRIDA trial with iadademstat in combination with gilteritinib in relapsed/refractory FLT3-mutant AML patientsResearch and development (R&D) expenses of $3.9 and $16.6 million for the quarter and twelve months ended December 31, 2023, respectively MADRID, Spain and BOSTON, Feb. 26, 2024 (GLOBE NEWSWIRE) -- Oryzon Genomics, S.A. (ISIN Code: ES0167733015, ORY), a clinical-stage biopharmaceutical company leveraging epigenetics to develop therapies in diseases with a strong unmet medical need, today reported financial results for the fourth quarter ended December 31, 2023 and provided a corporate update on recent developments. Dr Carlos Buesa, Oryzon’s Chief Executive Officer, said: “Oryzon continued with a strong path in its clinical programs in the fourth quarter. In CNS, we recently presented topline results for our Phase IIb PORTICO trial evaluating vafidemstat as a treatment for Borderline Personality Disorder (BPD). Although the primary endpoints were not met, two important secondary endpoints evaluating improvement in overall BPD disease severity and in agitation/aggression reached nominal statistical significance, and the results across all the primary and secondary efficacy endpoints favored vafidemstat over placebo. This is the first time, to the best of our knowledge, that a large, randomized Phase II trial in BPD had two secondary endpoints that met statistical significance reflecting clinically meaningful improvements in overall BPD severity and in agitation/aggression. In a disease with currently no approved drugs, and no established regulatory endpoints yet, PORTICO’s results across these two important endpoints are paving the way, in our opinion, to define a registrational Phase III trial, based for the first time on a well-controlled study that has enrolled a truly representative real-world BPD population. Once the full analysis is completed, the company will request an End-of-Phase II meeting with the FDA to discuss the design of a Phase III. Our Phase IIb trial with vafidemstat in schizophrenia, EVOLUTION, has also continued to enroll patients. We continue working for a future submission of an IND to initiate HOPE in 2024, the first randomized Phase I/II personalized medicine trial with an LSD1 inhibitor, in Kabuki Syndrome patients.” Dr Buesa continued: “In oncology, we also continued to make progress this quarter in both iadademstat’s ongoing clinical trials. In the FRIDA trial in combination with gilteritinib in relapsed/refractory FLT3-mutant AML patients, the second cohort is fully enrolled and ongoing, and the company’s assessment on the initial preliminary data looks very promising when compared to gilteritinib alone in historical data. We expect to communicate some preliminary data at the EHA Conference next June in Madrid. The collaborative trial with the Fox Chase Cancer Center (FCCC) in combination with paclitaxel in neuroendocrine tumors is also actively recruiting patients. In addition, we are expanding iadademstat’s clinical development through additional clinical trials under our CRADA with the NCI and through investigator-initiated studies in SCLC in combination with ICIs and in first line AML in combination with venetoclax and azacitidine.” Dr Buesa added: “While we have experienced a clear advance in our clinical pipeline, on the financial side, the company has continued its budgetary discipline. This, and the combination of non-dilutive funds (private and public grants and loans from commercial Spanish banks) with the withdrawal of €10 million from our €45 million Convertible Bond program allows us to extend the runway until 2025 and to focus now on the next conversations with the FDA and EMA and our clinical execution.” Fourth Quarter and Recent Highlights Vafidemstat in large multifactorial CNS indications: Topline results from PORTICO, a multicenter, double-blind, randomized, placebo-controlled Phase IIb conducted in the U.S. and EU to evaluate the efficacy and safety of vafidemstat in BPD patients, were reported on January 5, 2024. The primary endpoints, improvement in Borderline Personality Disorder Checklist (BPDCL) and in agitation/aggression by the Clinical Global Impression – Severity Agitation/Aggression (CGI-S A/A), did not reach statistical significance. However, nominal statistical significance was achieved on the secondary endpoint Borderline Evaluation of Severity (BEST), an overall measure of BPD disease severity, at weeks 8-12 (p = 0.042), with a relative reduction observed in the vafidemstat-treated group over the placebo group of 28.9%. Nominal statistical significance was also achieved on the secondary endpoint State-Trait Anger Expression Inventory 2 (STAXI-2) Trait Anger, a measure of agitation and aggression, at weeks 8-12 (p = 0.026), with a relative reduction observed in the vafidemstat-treated group over the placebo group of 46.7%. Results across all primary and secondary efficacy endpoints consistently favored vafidemstat over placebo. Global Statistical Test (GST p-values) confirmed a consistent trend across efficacy endpoints. Vafidemstat was safe and well-tolerated. Adverse events (AEs) were generally consistent with the safety profile of vafidemstat seen to date, with no new safety findings. Based on the efficacy and safety results, Oryzon intends to request an end-of-Phase II meeting with the FDA to discuss plans for a registrational Phase III study for the treatment of BPD. The company is currently completing the full data analysis and plans to provide a full data presentation at a psychiatric conference later this year, as well as in a peer-reviewed journal publication.The EVOLUTION Phase IIb clinical trial with vafidemstat in patients with schizophrenia continues to enroll patients. This Phase IIb study aims to evaluate the efficacy of vafidemstat on negative symptoms and cognitive impairment in patients with schizophrenia. This project is partially financed with public funds from the Spanish Ministry of Science and Innovation and is being carried out in various Spanish hospitals. Vafidemstat in monogenic CNS indications: We continue the preparations of a new precision medicine trial in Kabuki Syndrome (KS). The company is in a dialogue with the regulatory agencies to refine the final design of this trial and expects to submit an IND for HOPE to the U.S. Food and Drug Administration (FDA) in 2024. Iadademstat in oncology: FRIDA, an open-label, multicenter Phase Ib clinical trial of iadademstat in combination with gilteritinib in patients with relapsed/refractory (R/R) Acute Myeloid Leukemia (AML) harboring a FMS-like tyrosine kinase mutation (FLT3mut+), continues to enroll patients. The first cohort has been completed (six patients), and the combination was safe and showed strong antileukemic activity. The second cohort (six patients) is fully enrolled and ongoing. The primary objectives of the trial are to evaluate the safety and tolerability of iadademstat in combination with gilteritinib in patients with FLT3mut+ R/R AML and to establish the Recommended Phase 2 Dose (RP2D) for this combination. Secondary objectives include the evaluation of the treatment efficacy, measured as the rate of complete remission and complete remission with partial hematological recovery (CR/CRh), the Duration of Responses (DoR), and the assessment of Measurable Residual Disease (MRD). The study is being conducted in the U.S. and will accrue up to approximately 45 patients. If successful, Oryzon and the FDA have agreed to hold a meeting to discuss the best plan to further develop this combination in this much-in-need AML population.The Company is further expanding the clinical development of iadademstat in AML through an Investigator-initiated study (IIS). This trial will be a Phase Ib dose-finding study to evaluate iadademstat in combination with venetoclax and azacitidine in first-line AML patients, led by Oregon Health & Science University (OHSU). The trial received FDA IND approval in 4Q2023 and is expected to begin enrolling patients in 1Q2024.The collaborative Phase II basket trial of iadademstat in combination with paclitaxel in platinum R/R small cell lung cancer (SCLC) and extrapulmonary high-grade neuroendocrine tumors (NET trial) continues to enroll patients. This trial is being conducted in the U.S. under a collaborative clinical research agreement with the FCCC, under which the FCCC will be conducting different collaborative combination clinical trials with iadademstat, with Oryzon providing funding, the drug, and technical expertise.A new clinical trial of iadademstat in combination with an immune checkpoint inhibitor (ICI) in first-line metastatic SCLC, which will be conducted under the Cooperative Research and Development Agreement (CRADA) signed with the National Cancer Institute (NCI) in the United States, is under preparation. This trial will be led by the Memorial Sloan Kettering Cancer Center (MSKCC), which plans to file the IND with the FDA in 1Q2024.The STELLAR trial, a randomized, multicenter Phase Ib/II study of iadademstat plus a checkpoint inhibitor in first-line extensive-stage SCLC, will be informed and refined from the findings of the CRADA-MSKCC trial in the same space and with the same design that is expected to start in 1Q2024, as mentioned above. The company believes that STELLAR could potentially support an application for accelerated approval. Earlier stage programs: ORY-4001, Oryzon’s highly selective histone deacetylase 6 (HDAC6) inhibitor nominated as a clinical candidate for the treatment of certain neurological diseases such as Charcot-Marie-Tooth disease (CMT), Amyotrophic Lateral Sclerosis (ALS) and others, is progressing through IND enabling studies to prepare it for clinical studies. The Company recently announced that is has received a 0.5 million USD grant from the ALS Association in the U.S. to support the regulatory preclinical development of ORY-4001 for ALS. ORY-4001 has been previously shown to reverse disease progression symptoms in a CMT mice model which reliably recapitulates many of the symptoms of this condition in humans, improving myelination and restoring axon integrity in the sciatic nerve, and improving compound muscle action potential and nerve conduction. These results are fruit of a collaboration entered in 2022 between Oryzon and the CMT Research Foundation (CMTRF), a U.S.-based patient-led, non-profit organization focused on delivering treatments and cures for CMT.Oryzon has received two new grants to further explore the role of epigenetic targets in the treatment of neuronal pathologies. These are two collaborative projects with public research centers, focused on the discovery and validation of novel biomarkers and epigenetic targets for the treatment of neuronal pathologies. The projects have a global budget of 2.3 million euros, of which Oryzon will receive up to 1.4 million euros. Financial Update: Fourth Quarter 2023 Financial Results Research and development (R&D) expenses were $3.9 and $16.6 million for the quarter and twelve months ended December 31, 2023, respectively, compared to $5.0 and $18.1 million for the quarter and twelve months ended December 31, 2022. General and administrative expenses were $1.2 and $4.2 million for the quarter and twelve months ended December 31, 2023, respectively, compared to $1.2 and $4.8 million for the quarter and twelve months ended December 31, 2022. Net losses were $1.4 and $5.0 million for the quarter and twelve months ended December 31, 2023, respectively, compared to $1.6 and $5.9 million for the quarter and twelve months ended December 31, 2022. The result is as expected, given the biotechnology business model where companies in the development phase typically have a long-term maturation period for products, and do not have recurrent income. Negative net result was $3.7 million (–$0.064 per share) for the twelve months ended December 31, 2023, compared to a negative net result of $4.5 million (–$0.085 per share) for the twelve months ended December 31, 2022 Cash, cash equivalents and marketable securities totaled $13.5 million as of December 31, 2023. ORYZON GENOMICS, S.A.BALANCE SHEET DATA (AUDITED)1(Amounts in thousands US $) December 31st, 2023 December 31st, 2022 Cash and cash equivalents13,544 22,737Marketable securities0 0Total Assets118,125 110,606 Deferred revenue12 0Total Stockholders' equity90,361 77,405 ORYZON GENOMICS, S.A. STATEMENTS OF OPERATIONS (AUDITED)1 (US $, amounts in thousands except per share data) Three Months Ended December 31st Twelve Months Ended December 31st 20232022 20232022 Collaboration Revenue 00 00 Operating expenses: Research and Development 3,8675,033 16,63118,050 General and administrative 1,1871,249 4,2474,822 Total operating expenses 5,0546,282 20,87822,872 Loss from Operations -5,054-6,282 -20,878-22,872 Other income, net 3,6194,693 15,85117,016 Net Loss -1,435-1,589 -5,027-5,856 Net Financial & Tax -468-863 1,3221,342 Net Result -1,903-2,452 -3,705-4,514 Loss per share allocable to common stockholders: Basic -0.03-0.05 -0.06-0.08 Weighted average Shares outstanding Basic 58,451,07054,284,176 57,616,23653,336,257 1 Spanish GAAP * Exchange Euro/Dollar (1.1050 for 2023 and 1.0666 in 2022) About OryzonFounded in 2000 in Barcelona, Spain, Oryzon (ISIN Code: ES0167733015) is a clinical stage biopharmaceutical company and the European leader in epigenetics, with a strong focus on personalized medicine in CNS disorders and oncology. Oryzon’s team is composed of highly qualified professionals from the pharma industry located in Barcelona, Boston, and San Diego. Oryzon has an advanced clinical portfolio with two LSD1 inhibitors, vafidemstat in CNS and iadademstat in oncology, in several Phase II clinical trials. The company has other pipeline assets directed against other epigenetic targets like HDAC-6, where ORY-4001 has been nominated as clinical candidate for the treatment of certain neurological disorders such as CMT and ALS. In addition, Oryzon has a strong platform for biomarker identification and target validation for a variety of malignant and neurological diseases. For more information, visit www.oryzon.com About Iadademstat Iadademstat (ORY-1001) is a small oral molecule, which acts as a highly selective inhibitor of the epigenetic enzyme LSD1 and has a powerful differentiating effect in hematologic cancers (see Maes et al., Cancer Cell 2018 Mar 12; 33 (3): 495-511.e12.doi: 10.1016 / j.ccell.2018.02.002.). A FiM Phase I/IIa clinical trial with iadademstat in R/R AML patients demonstrated the safety and good tolerability of the drug and preliminary signs of antileukemic activity, including a CRi (see Salamero et al, J Clin Oncol, 2020, 38(36): 4260-4273. doi: 10.1200/JCO.19.03250). Iadademstat has shown encouraging safety and efficacy data in combination with azacitidine in a Phase IIa trial in elder 1L AML patients (ALICE trial) (see Salamero et al., ASH 2022 oral presentation). Iadademstat is currently being evaluated in combination with gilteritinib in the ongoing Phase Ib FRIDA trial in patients with relapsed/refractory AML with FLT3 mutations. Beyond hematological cancers, the inhibition of LSD1 has been proposed as a valid therapeutic approach in some solid tumors such as small cell lung cancer (SCLC), neuroendocrine tumors (NET), medulloblastoma and others. In a Phase IIa trial in combination with platinum/etoposide in second line ED-SCLC patients (CLEPSIDRA trial), preliminary activity and safety results have been reported (see Navarro et al., ESMO 2018 poster). Iadademstat is being evaluated in a collaborative Phase II basket study with the Fox Chase Cancer Center (FCCC) in combination with paclitaxel in R/R neuroendocrine carcinomas, and the company is preparing a new trial in combination with immune checkpoint inhibitors (ICI) in SCLC. Oryzon has entered into a Cooperative Research and Development Agreement (CRADA) with the U.S. National Cancer Institute (NCI) to collaborate on potential further clinical development of iadademstat in different types of solid and hematological cancers; a first trial in combination with ICI in SCLC is under preparation. In total iadademstat has been dosed so far to more than 130 cancer patients in four clinical trials. Iadademstat has orphan drug designation for SCLC in the US and for AML in the US and EU. About Vafidemstat Vafidemstat (ORY-2001) is an oral, CNS-optimized LSD1 inhibitor. The molecule acts on several levels: it reduces cognitive impairment, including memory loss and neuroinflammation, and at the same time has neuroprotective effects. In animal studies vafidemstat not only restores memory but reduces the exacerbated aggressiveness of SAMP8 mice, a model for accelerated aging and Alzheimer’s disease (AD), to normal levels and also reduces social avoidance and enhances sociability in murine models. In addition, vafidemstat exhibits fast, strong, and durable efficacy in several preclinical models of multiple sclerosis (MS). Oryzon has performed two Phase IIa clinical trials in aggressiveness in patients with different psychiatric disorders (REIMAGINE) and in aggressive/agitated patients with moderate or severe AD (REIMAGINE-AD), with positive clinical results reported in both. Additional finalized Phase IIa clinical trials with vafidemstat include the ETHERAL trial in patients with Mild to Moderate AD, where a significant reduction of the inflammatory biomarker YKL40 has been observed after 6 and 12 months of treatment, and the pilot, small-scale SATEEN trial in Relapse-Remitting and Secondary Progressive MS, where anti-inflammatory activity has also been observed. Vafidemstat has also been tested in a Phase II in severe Covid-19 patients (ESCAPE) assessing the capability of the drug to prevent ARDS, one of the most severe complications of the viral infection, where it showed significant anti-inflammatory effects in severe Covid-19 patients. Vafidemstat is being investigated in neuropsychiatric disorders in two double-blind, randomized, placebo-controlled Phase IIb trials: one in schizophrenia, named EVOLUTION (recruitment ongoing), and another one in Borderline Personality disorder (BPD), named PORTICO, recently finalized, with topline data and in the process of completing the full data analysis. Based on PORTICO’s topline results, the company is planning to request an End-of-Phase II meeting with the FDA to discuss options for a registrational Phase III trial in BPD. The company is also deploying a CNS precision medicine approach with vafidemstat in genetically-defined patient subpopulations of certain CNS disorders and is preparing a clinical trial in Kabuki Syndrome patients. The company is also exploring the clinical development of vafidemstat in other neurodevelopmental syndromes. FORWARD-LOOKING STATEMENTS This communication contains, or may contain, forward-looking information and statements about Oryzon, including financial projections and estimates and their underlying assumptions, statements regarding plans, objectives and expectations with respect to future operations, capital expenditures, synergies, products and services, and statements regarding future performance. Forward-looking statements are statements that are not historical facts and are generally identified by the words “expects,” “anticipates,” “believes,” “intends,” “estimates” and similar expressions. Although Oryzon believes that the expectations reflected in such forward-looking statements are reasonable, investors and holders of Oryzon shares are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of Oryzon that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include those discussed or identified in the documents sent by Oryzon to the Spanish Comisión Nacional del Mercado de Valores (CNMV), which are accessible to the public. Forward-looking statements are not guarantees of future performance and have not been reviewed by the auditors of Oryzon. You are cautioned not to place undue reliance on the forward-looking statements, which speak only as of the date they were made. All subsequent oral or written forward-looking statements attributable to Oryzon or any of its members, directors, officers, employees or any persons acting on its behalf are expressly qualified in their entirety by the cautionary statement above. All forward-looking statements included herein are based on information available to Oryzon on the date hereof. Except as required by applicable law, Oryzon does not undertake any obligation to publicly update or revise any forward‐looking statements, whether as a result of new information, future events or otherwise. This press release is not an offer of securities for sale in the United States or any other jurisdiction. Oryzon’s securities may not be offered or sold in the United States absent registration or an exemption from registration. Any public offering of Oryzon’s securities to be made in the United States will be made by means of a prospectus that may be obtained from Oryzon or the selling security holder, as applicable, that will contain detailed information about Oryzon and management, as well as financial statements. IR, USIR & Media, EuropeSpainOryzonAshley R. RobinsonSandya von der WeidPatricia Cobo/Mario CorderaEmili TorrellLifeSci Advisors, LLCLifeSci Advisors, LLCAtreviaChief Business Officer+1 617 430 7577+41 78 680 05 38+34 91 564 07 25+34 673 33 97 65+34 93 515 1313arr@lifesciadvisors.comsvonderweid@lifesciadvisors.compcobo@atrevia.commcordera@atrevia.cometorrell@oryzon.com

Reported $380.8 million in net product revenue for the full year 2023, including $108.4 million in the fourth quarter Delivered $49.3 million in net income for the full year 2023, including $4.7 million in the fourth quarter, and ended the year with cash, cash equivalents and short-term investments of $371.4 million 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 fourth quarter and full year ended December 31, 2023. “In 2023, we made significant strides towards transforming the way ALS is treated. We delivered RELYVRIO, also known as ALBRIOZA and AMX0035, the first and only ALS therapy that has been shown to slow disease progression, help maintain functional independence, and extend overall survival in the same clinical trial, to thousands of people living with ALS in North America,” said Joshua Cohen, co-CEO of Amylyx. “As we reflect on the many stories that we have heard from people living with ALS who are taking RELYVRIO, we are working with urgency to continue expanding our U.S. and international presence in 2024 and bringing RELYVRIO to more people living with ALS.” “We look forward to sharing topline data from our Phase 3 PHOENIX trial during or before the second quarter of 2024. PHOENIX will provide additional efficacy and safety data in a larger population of people living with ALS, building on the robust and positive results observed in the CENTAUR study,” said Justin Klee, co-CEO of Amylyx. “We also remain focused on advancing our pipeline, which includes studying AMX0035 in Progressive Supranuclear Palsy in the Phase 3 ORION trial. We look forward to several expected upcoming milestones for our pipeline in 2024, including data from our Phase 2 HELIOS trial in Wolfram syndrome and our antisense oligonucleotide, AMX0114, entering the clinic.” Full Year 2023 and Recent Business Highlights: Commercial launches of RELYVRIO® in the U.S. and ALBRIOZA™ in Canada, also known as AMX0035, continued to progress, and eligible people living with ALS in multiple countries are also accessing RELYVRIO through early access pathways. Net product revenue for the three months ended December 31, 2023 was $108.4 million, compared to net product revenue of $102.7 million for the three months ended September 30, 2023. The vast majority of Amylyx’ net product revenue is generated in the U.S.; revenue in Canada and from named patient sales programs in international markets represented an important source of revenue growth in three months ended December 31, 2023 relative to the Company’s financial results for the three months ended September 30, 2023. Amylyx announced the first patient dosed in the Global Phase 3 ORION Study of AMX0035 in Progressive Supranuclear Palsy (PSP). ORION 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. Approximately 600 participants will be enrolled across North America, Europe, and Japan. The first participant was dosed in December 2023, and topline results are anticipated in 2025 or 2026. Amylyx continues to progress its R&D programs. The Company announced completion of enrollment in the HELIOS study, a Phase 2 clinical trial of AMX0035 for the treatment of Wolfram syndrome and continues to expect data from the study in 2024. The Company is also working on a novel composite diagnostic test to assist in diagnosing ALS earlier. Additionally, Amylyx is working on a new taste-masked formulation of RELYVRIO that may allow for new intellectual property. Amylyx added new members to its executive leadership team and U.S. commercial leadership team. In November 2023, the Company announced the appointment of Camille L. Bedrosian, MD, as Chief Medical Officer. Dr. Bedrosian has nearly 30 years of experience addressing unmet medical needs for people with rare and serious diseases through successful clinical and translational research programs. In addition, during 2024, Linda Arsenault joined as the Company’s new Chief Human Resources Officer and Dan Monahan joined as General Manager and Head of U.S. Commercial Markets. Ms. Arsenault has over 30 years of human resources leadership experience, including in the biopharmaceutical sector, most recently from Sunovion Pharmaceuticals where she served as Chief Human Resources Officer. Mr. Monahan has over 20 years of experience in sales, marketing, and market access, including his most recent position as VP of CNS Marketing and Portfolio Strategy at Otsuka Pharmaceutical Companies. A post hoc survival analysis comparing the CENTAUR clinical trial to historical clinical trial control was published in the Annals of Clinical and Translational Neurology. The results of this post hoc analysis demonstrated that the median overall survival was 10.4 months longer in the CENTAUR AMX0035 group than in the historical clinical trial control group. Post hoc analyses on CENTAUR trial participants were published in Journal of Neurology, Neurosurgery and Psychiatry. The results of the post hoc analyses demonstrated a significant reduction in plasma concentrations of YKL-40 (also known as chitinase-3-like protein 1) and the systemic inflammatory biomarker C-reactive protein (CRP), two plasma neuroinflammatory biomarkers in ALS, over 24 weeks, with reductions observed as early as Week 12 in participants from the CENTAUR trial. Data on RELYVRIO and AMX0114, the Company’s investigational antisense oligonucleotide targeting calpain-2, were presented at the 34th International Symposium on ALS/MND. An update on kinetic profiling experiments of AMX0114 was presented as well as results from a collaboration with Dr. Sami Barmada and his team at the University of Michigan School of Medicine in which the impact of AMX0114 on survival was evaluated in human iPSC-derived motor neurons with an ALS associated mutation in TDP43. The Company is advancing AMX0114 through investigational new drug (IND) enabling studies and the goal is to enter the clinic during 2024. Additional information, including copies of each of the posters presented at the event, are available in the in the “Publications and Presentations” section of the Amylyx website. Financial Results for the Fourth Quarter and Year Ended December 31, 2023 Net product revenue: Net product revenue was $108.4 million for the three months ended December 31, 2023, compared to net product revenue of $21.9 million for the same period in 2022. Net product revenue for the year ended December 31, 2023 was $380.8 million, compared to net product revenue of $22.2 million for the same period in 2022. The increase was primarily driven by units of RELYVRIO sold in the U.S. following regulatory approval in late September 2022. Cost of Sales: Cost of sales were $9.4 million in the three months ended December 31, 2023, compared to cost of sales of $2.8 million for the same period in 2022. For the year ended December 31, 2023, cost of sales were $25.4 million, compared to cost of sales of $3.0 million for the year ended December 31, 2022. R&D Expenses: Research and development expenses for the fourth quarter of 2023 were $44.9 million, compared to $22.8 million for the same period in 2022, and $128.2 million for the year ended December 31, 2023 compared to $93.5 million for the year ended December 31, 2022. 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 related to the initiation of the Phase 3 ORION trial of AMX0035 in PSP, and an increase in preclinical development activities. SG&A Expenses: Selling, general, and administrative expenses for the fourth quarter of 2023 were $52.2 million, compared to $40.8 million for the same period in 2022 and $188.4 million for the year ended December 31, 2023, compared to $127.1 million for the year ended December 31, 2022. The increase was primarily driven by higher personnel-related expenses due to added headcount to support the launch, commercialization initiatives, and operations as a public company. Net Income: Net income for the three months ended December 31, 2023 was $4.7 million, or $0.07 on a fully diluted per share basis, compared to a net loss of $42.7 million, or $0.65 per share for the same period in 2022. Net income for the year ended December 31, 2023 was $49.3 million, or $0.70 on a fully diluted per share basis, compared with a net loss of $198.4 million, or $3.39 per share for the year ended December 31, 2022. Cash Position: Cash, cash equivalents, and short-term investments were $371.4 million at December 31, 2023, compared to $355.0 million at September 30, 2023. Investor Conference Call Information Amylyx’ management team will host a conference call and webcast today, February 22, 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, . 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 RELYVRIO®/ALBRIOZA™/AMX0035 RELYVRIO® (also known as AMX0035), an oral, fixed-dose combination of sodium phenylbutyrate and taurursodiol (known as ursodoxicoltaurine outside of the U.S.), is approved to treat amyotrophic lateral sclerosis (ALS) in adults in the U.S. and approved with conditions as ALBRIOZA™ for the treatment of ALS in Canada. AMX0035 is being studied as an investigational drug in several other regions for the potential treatment of ALS and other neurodegenerative diseases. The formulation of RELYVRIO, ALBRIOZA, and AMX0035 are identical. RELYVRIO® (sodium phenylbutyrate and taurursodiol) Safety Information for United States WARNINGS AND PRECAUTIONS Risk in Patients with Enterohepatic Circulation Disorders, Pancreatic Disorders, or Intestinal Disorders RELYVRIO contains taurursodiol, which is a bile acid. In patients with disorders that interfere with bile acid circulation, there may be an increased risk for worsening diarrhea, and patients should be monitored appropriately for this adverse reaction. Pancreatic insufficiency, intestinal malabsorption, or intestinal diseases that may alter the concentration of bile acids may also lead to decreased absorption of either of the components of RELYVRIO. Because different enterohepatic circulation, pancreatic, and intestinal disorders have varying degrees of severity, consider consulting with a specialist. Patients with disorders of enterohepatic circulation (e.g., biliary infection, active cholecystitis), severe pancreatic disorders (e.g., pancreatitis), and intestinal disorders that may alter concentrations of bile acids (e.g., ileal resection, regional ileitis) were excluded from the study; therefore, there is no clinical experience in these conditions. Use in Patients Sensitive to High Sodium Intake RELYVRIO has a high salt content. Each initial daily dosage of 1 packet contains 464 mg of sodium; each maintenance dosage of 2 packets daily contains 928 mg of sodium. In patients sensitive to salt intake (e.g., those with heart failure, hypertension, or renal impairment), consider the amount of daily sodium intake in each dose of RELYVRIO and monitor appropriately. ADVERSE REACTIONS The most common adverse reactions (at least 15% and at least 5% greater than placebo) with RELYVRIO were diarrhea, abdominal pain, nausea, and upper respiratory tract infection. Gastrointestinal-related adverse reactions occurred throughout the study but were more frequent during the first 3 weeks of treatment. Please click here for RELYVRIO Full U.S. Prescribing Information. About Amylyx Pharmaceuticals Amylyx Pharmaceuticals, Inc. is committed to supporting and creating more moments for the neurodegenerative community through the discovery and development of innovative new treatments. Amylyx is headquartered in Cambridge, Massachusetts and has operations in Canada, EMEA, and Japan. 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 ALS and other neurodegenerative diseases including Wolfram syndrome and PSP; the Company’s beliefs regarding the benefits of AMX0035 in ALS and other neurodegenerative diseases, the potential of AMX0035 to be a foundational therapy for ALS and a potential, future cure; the ongoing commercialization of RELYVRIO and ALBRIOZA; the potential to expand global approvals for AMX0035 in ALS and other neurodegenerative diseases; expectations regarding the timing of the announcement of results from the Phase 3 PHOENIX trial of AMX0035 for the treatment of ALS, the Company’s Phase 3 ORION trial of AMX0035 for the treatment of PSP, and the Company’s Phase 2 HELIOS trial of AMX0035 for the treatment of Wolfram syndrome; the potential continued market acceptance and market opportunity for RELYVRIO and ALBRIOZA and opportunities for growth; the potential for new pipeline programs and clinical indications for AMX0035; statements regarding regulatory developments; the Company’s expectations with respect to its progress through IND enabling studies of AMX0114 and other advancements in its pipeline; the Company’s expectations regarding its financial performance; and expectations regarding the Company’s 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 successfully commercialize RELYVRIO in the United States and ALBRIOZA in Canada, Amylyx’ ability to execute on its commercial and regulatory strategy, regulatory developments, expectations regarding the timing of results of the global Phase 3 PHOENIX trial of AMX0035 for the treatment of ALS, Amylyx’ ability to fund operations, and the impact that global macroeconomic uncertainty, geopolitical instability and public health events, such as COVID-19, 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) December 31, 2023 2022 Assets Cash, cash equivalents and short-term investments $ 371,362 $ 346,945 Accounts receivable, net 40,050 15,306 Inventories 83,280 9,769 Prepaid expenses and other current assets 14,931 10,113 Other assets 7,831 9,320 Total assets $ 517,454 $ 391,453 Liabilities and Stockholders’ Equity Accounts payable and accrued expenses $ 79,785 $ 44,569 Other liabilities 4,237 6,277 Total liabilities 84,022 50,846 Stockholders’ equity 433,432 340,607 Total liabilities, redeemable convertible preferred stock and stockholders' equity $ 517,454 $ 391,453 AMYLYX PHARMACEUTICALS, INC. CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS UNAUDITED (in thousands, except share and per share data) Three Months Ended December 31, Year Ended December 31, 2023 2022 2023 2022 Product revenue, net $ 108,449 $ 21,885 $ 380,786 $ 22,230 Operating expenses: Cost of sales 9,360 2,821 25,441 2,993 Research and development 44,914 22,813 128,187 93,450 Selling, general and administrative 52,241 40,844 188,356 127,128 Total operating expenses 106,515 66,478 341,984 223,571 Income (loss) from operations 1,934 (44,593 ) 38,802 (201,341 ) Other income, net 4,542 2,468 15,495 3,740 Income (loss) before income taxes 6,476 (42,125 ) 54,297 (197,601 ) Provision for income taxes 1,745 579 5,026 774 Net income (loss) $ 4,731 $ (42,704 ) $ 49,271 $ (198,375 ) Net income (loss) per share Basic $ 0.07 $ (0.65 ) $ 0.73 $ (3.39 ) Diluted $ 0.07 $ (0.65 ) $ 0.70 $ (3.39 ) Weighted-average shares used in computing net income (loss) per share Basic 67,414,669 65,416,712 67,234,465 58,495,587 Diluted 69,196,421 65,416,712 69,991,340 58,495,587