Avexitide

Recruitment of the pivotal Phase 3 LUCIDITY trial of avexitide in PBH is complete; continue to expect to randomize and dose last eligible participants in Q1 2026, with topline data anticipated in Q3 2026 Cash runway expected to fund operations through potential avexitide commercialization and into 2028 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 and business results for the fourth quarter and full year ended December 31, 2025. “2025 was a year of meaningful advancement for Amylyx’s pivotal avexitide program in post-bariatric hypoglycemia, as well as progress across our broader pipeline,” said Joshua Cohen and Justin Klee, Co-CEOs of Amylyx. “In 2026, our primary focus is on our Phase 3 LUCIDITY trial of avexitide in PBH. With recruitment of LUCIDITY complete, we are on track to complete enrollment this month and continue to expect topline data in Q3 2026. We designed LUCIDITY with the goal of replicating and building on the robust body of evidence demonstrating statistically significant reductions in hypoglycemic events observed in five prior clinical trials of avexitide in PBH. We continue to be encouraged by the high participant interest and broad engagement seen across the LUCIDITY trial sites.” “Looking ahead, we have a clear trajectory toward potentially delivering the first FDA-approved therapy to the PBH community. Supported by a cash runway extending into 2028, we remain focused on disciplined execution as we continue to actively prepare for a regulatory submission and build our commercial infrastructure to support potential commercialization in 2027,” continued Mr. Cohen and Mr. Klee. Fourth Quarter and Recent Updates: Amylyx announced the selection of AMX0318, a novel glucagon-like peptide-1 (GLP-1) receptor antagonist for long-acting administration, as a development candidate for post-bariatric hypoglycemia (PBH) and other rare diseases. AMX0318 was selected as a development candidate after demonstrating robust preclinical and chemical properties, including a favorable pharmacokinetic pro may support long-acting administration, a robust chemical stability profile, strong in vitro potency, evidence of in vivo activity and tolerability, and high solubility. AMX0318 was identified through a research collaboration with Gubra A/S, a company specializing in peptide-based drug discovery and preclinical contract research services. Amylyx presented early safety and tolerability data from Cohort 1 of its Phase 1 LUMINA trial of AMX0114 at the 36 th International Symposium on ALS/MND (MNDA) in December 2025. AMX0114 is an investigational antisense oligonucleotide (ASO) targeting calpain-2 with U.S. Food and Drug Administration (FDA) Fast Track Designation for the potential treatment of amyotrophic lateral sclerosis (ALS). AMX0114 was generally well-tolerated in LUMINA trial participants enrolled in Cohort 1 (n=12), with no treatment-related serious adverse events (SAEs). Upcoming Expected Milestones: Recruitment of the pivotal Phase 3 LUCIDITY trial of avexitide in PBH is complete. Amylyx continues to expect to randomize and dose the last eligible participants this month with topline data expected in Q3 2026, and, if approved, a commercial launch in 2027. Avexitide is an investigational, first-in-class GLP-1 receptor antagonist with FDA Breakthrough Therapy Designation in PBH. LUCIDITY is a 16-week, multicenter, randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of avexitide in approximately 75 participants with PBH following Roux-en-Y gastric bypass (RYGB) surgery. LUCIDITY is evaluating the FDA-agreed-upon primary outcome of reduction in the composite of Level 2 and Level 3 hypoglycemic events through Week 16. Participants who complete the 16-week double-blind period are eligible to enter a 32-week open-label extension (OLE) period. Completion of enrollment of Cohort 2 (n=12) of the Phase 1 LUMINA clinical trial of AMX0114 in ALS is expected in March 2026 and presentation of biomarker data from Cohort 1 (n=12) is expected in the first half of 2026 . The LUMINA trial is a randomized, double-blind, placebo-controlled, multiple ascending dose clinical trial of AMX0114 in people living with ALS, with Cohort 1 investigating the first and lowest of four doses being evaluated in the trial. LUMINA is evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of AMX0114 in people living with ALS and assessing both novel and broadly researched ALS biomarkers, including change from baseline in neurofilament light chain (NfL) levels. Investigational New Drug (IND)-enabling studies for AMX0318 are underway with an IND filing targeted for 2027. AMX0318 has completed extensive preclinical evaluation, including stability, solubility, potency, in vivo pharmacokinetics and pharmacodynamics, and in vivo tolerability studies. Financial Results for the Fourth Quarter and Year Ended December 31, 2025 R&D Expenses: Research and development expenses for the fourth quarter of 2025 were $21.2 million, compared to $22.9 million for the same period in 2024, and $90.4 million for the year ended December 31, 2025, compared to $104.1 million for the year ended December 31, 2024. The decrease was primarily due to a decrease in spending on AMX0035 for the treatment of ALS and progressive supranuclear palsy (PSP). The decrease was offset by increased spending related to the clinical development of avexitide in PBH. Research and development expenses include $1.6 million and $7.0 million of stock-based compensation expense for the quarter and year ended December 31, 2025, respectively, compared to $1.8 million and $8.8 million of stock-based compensation expense for the quarter and year ended December 31, 2024, respectively. SG&A Expenses: Selling, general, and administrative expenses for the fourth quarter of 2025 were $15.4 million, compared to $17.1 million for the same period in 2024 and $62.9 million for the year ended December 31, 2025, compared to $114.3 million for the year ended December 31, 2024. This decrease was primarily due to a decrease in consulting and professional services. Selling, general, and administrative expenses include $4.8 million and $20.7 million of stock-based compensation expense for the quarter and year ended December 31, 2025, respectively, compared to $5.0 million and $24.3 million of stock-based compensation expense for the quarter and year ended December 31, 2024, respectively. Net Loss: Net loss for the three months ended December 31, 2025 was $33.0 million, or $0.30 per share, compared to net loss of $37.5 million, or $0.55 per share for the same period in 2024. Net loss for the year ended December 31, 2025 was $144.7 million, or $1.53 per share, compared with net loss of $301.7 million, or $4.43 per share for the year ended December 31, 2024. Cash Position: Cash, cash equivalents, and short-term investments were $317.0 million at December 31, 2025, compared to $344.0 million at September 30, 2025. Based on its current operating plans, Amylyx expects its cash runway into 2028. Investor Conference Call Information Amylyx’s management team will host a conference call today, March 3 rd , 2026, 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 (888)-880-3330 (U.S. & Canada) or +1 (646)-357-8766 (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 Avexitide Avexitide is an investigational, first-in-class glucagon-like peptide-1 (GLP-1) receptor antagonist that has been evaluated in five Phase 1 and Phase 2 clinical trials 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 inhibit the effect of GLP-1 to mitigate hypoglycemia by decreasing insulin secretion and stabilizing blood glucose levels. In PBH, excessive GLP-1 can lead to the hypersecretion of insulin and subsequent debilitating hypoglycemic events. In two Phase 2 PBH clinical 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) Post-bariatric hypoglycemia (PBH) is a condition that is estimated to affect approximately 8% of people in the U.S. who have undergone the two most common types of bariatric surgery, sleeve gastrectomy and Roux-en-Y gastric bypass (approximately 160,000 people in the U.S.). PBH is thought to be caused by an excessive glucagon-like peptide-1 (GLP-1) response leading to hypoglycemia and impaired quality of life. PBH can cause debilitating hypoglycemic events associated with inadequate supply of glucose to the brain, known as neuroglycopenia. Clinical manifestations can include impaired cognition, loss of consciousness, and seizures. PBH is also associated with a high degree of disability that can result in major disruptions to independent living. There are no approved therapies for PBH. About the LUCIDITY Trial LUCIDITY ( NCT06747468 ) is an approximately 75-participant, multicenter, randomized, double-blind, placebo-controlled Phase 3 clinical trial evaluating the efficacy and safety of avexitide in participants with PBH following Roux-en-Y gastric bypass (RYGB) surgery. The Phase 3 trial is being conducted at 21 sites in the U.S. Participants will be randomized 3:2 to receive either 90 mg of avexitide subcutaneously once daily or placebo. The trial includes an up to six-week screening period, including a three-week run-in period, and a 16-week double-blind treatment period. Participants who complete the double-blind period will be eligible to enter an open-label extension (OLE) period with a duration of 32 weeks. The primary efficacy objective of LUCIDITY will evaluate the FDA-agreed upon primary outcome of reduction in the composite of Level 2 and Level 3 hypoglycemic events through Week 16. Safety and tolerability will also be evaluated. About Amylyx Pharmaceuticals At Amylyx, our mission is to usher in a new era of treating diseases with high unmet needs. Where others see challenges, we see opportunities that we pursue with urgency, rigorous science, and unwavering commitment to the communities we serve. We are currently focused on four investigational therapies across several endocrine conditions and neurodegenerative diseases in which we believe they can make the greatest impact. 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 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’s expectations regarding: the potential of avexitide as a treatment for PBH; expectations regarding the timing for enrollment completion and topline data readout of the Phase 3 LUCIDITY trial of avexitide; expectations regarding timing for potential commercialization of avexitide; the potential for AMX0114 as a treatment for ALS, the expected timeline for cohort 1 biomarker data from the Phase 1 LUMINA clinical trial, and expectation for regulatory action; the therapeutic potential for AMX0318, the expected timeline for a potential IND submission for AMX0318; and Amylyx’s expectations regarding its financial performance, 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’s program development activities; Amylyx’s 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; Amylyx’s ability to fund operations, and the impact that global macroeconomic uncertainty, geopolitical instability, and public health events will have on Amylyx’s operations, as well as the risks and uncertainties set forth in Amylyx’s United States Securities and Exchange Commission (SEC) filings, including Amylyx’s Annual Report on Form 10-K for the year ended December 31, 2025, 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) December 31, 2025 2024 Assets Cash, cash equivalents and marketable securities $ 316,979 $ 176,501 Accounts receivable, net 88 447 Inventories — — Prepaid expenses and other current assets 6,604 12,484 Other assets 8,974 4,202 Total assets $ 332,645 $ 193,634 Liabilities and Stockholders’ Equity Accounts payable and accrued expenses $ 21,429 $ 26,888 Other liabilities 5,957 1,981 Total liabilities 27,386 28,869 Stockholders’ equity 305,259 164,765 Total liabilities and stockholders' equity $ 332,645 $ 193,634 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, 2025 2024 2025 2024 Product revenue, net $ — $ (665 ) $ — $ 87,371 Operating expenses: Cost of sales — — — 5,953 Cost of sales - inventory impairment and loss on firm purchase commitments — — — 118,680 Acquired in-process research and development — — — 36,203 Research and development 21,213 22,892 90,404 104,084 Selling, general and administrative 15,392 17,097 62,887 114,331 Restructuring expenses — — — 22,851 Total operating expenses 36,605 39,989 153,291 402,102 Loss from operations (36,605 ) (40,654 ) (153,291 ) (314,731 ) Other income, net 3,652 2,473 8,602 12,595 Loss before income taxes (32,953 ) (38,181 ) (144,689 ) (302,136 ) Provision (benefit) for income taxes 46 (635 ) 46 (393 ) Net loss $ (32,999 ) $ (37,546 ) $ (144,735 ) $ (301,743 ) Net loss per share - basic and diluted $ (0.30 ) $ (0.55 ) $ (1.53 ) $ (4.43 ) Weighted-average shares used in computing net loss per share - basic and diluted 109,841,882 68,593,499 94,565,567 68,142,158 Contacts Media Amylyx Media Team +1 (857) 320-6191 amylyxmediateam@amylyx.com Investors Lindsey Allen Amylyx Pharmaceuticals, Inc. +1 (857) 320-6244 Investors@amylyx.com

$Amylyx(AMLX)$1.公司概述AmylyxPharmaceuticals,Inc.（纳斯达克代码：AMLX）是一家总部位于美国马萨诸塞州剑桥的临床阶段生物制药公司，由JoshuaCohen和JustinKlee于2013年共同创立。公司秉承“为高度未满足需求的疾病开发创新疗法”的使命，专注于神经退行性疾病和内分泌疾病领域。2022年1月，Amylyx成功在纳斯达克上市，融资约1.5亿美元，为其研发管线提供了坚实资金支持。截至2025年9月30日，公司拥有约3.44亿美元现金及短期投资，预计可支撑运营至2028年，覆盖核心产品Avexitide的潜在批准与上市。公司团队规模约120人，核心管理层具备丰富的罕见病药物开发与商业化经验。2.研发管线总览Amylyx的研发管线围绕明确的疾病生物学机制构建，涵盖多个具有突破性潜力的在研药物。下图展示了公司目前的核心资产及开发阶段：3.Avexitide：首创GLP-1受体拮抗剂治疗餐后低血糖3.1作用机制与临床定位Avexitide是一种首创（first-in-class）的GLP-1受体拮抗剂，通过阻断GLP-1受体的过度激活，减少胰岛素分泌，从而预防餐后低血糖（PBH）。PBH常见于胃旁路术后患者，由于餐后GLP-1水平异常升高（可达正常人的10倍以上），导致胰岛素分泌失调，引发危险的低血糖事件。3.2临床数据亮点Avexitide已在多项2期临床试验中验证其疗效与安全性：在PHASE2PREVENT研究中，Avexitide30mg每日两次可使Level2低血糖减少40%（p=0.04），Level3减少23%（p=0.2）；60mg每日一次则分别减少60%（p=0.004）和56%（p=0.01）。在PHASE2B研究中，45mg每日两次使Level2减少57%（p=0.003），Level3减少68%（p=0.0003）；90mg每日一次分别减少53%（p=0.004）和66%（p=0.0003）。数据显示，Avexitide显著降低了低血糖事件，且效果呈剂量依赖性，总体降低超过50%，治疗作用在多个试验阶段均得到支持。在新近的探索性分析中，90mg每日一次可使2级和3级低血糖事件总体减少64%（p=0.0031）。该药物已获FDA突破性疗法认定，III期试验将评估90mg每日一次在PBH患者中的疗效，主要终点为复合低血糖事件的减少。3.3安全性特征在两项2期试验中，Avexitide总体耐受性良好，不良事件多为轻度至中度，最常见为注射部位反应、头痛、恶心。无治疗相关的严重不良事件，无受试者因不良事件退出。3.43期临床试验：LUCIDITY基于2期结果，Amylyx启动了全球性3期LUCIDITY试验，设计如下：人群：胃旁路术后PBH患者，尽管饮食管理仍有低血糖事件（每周≥1次）剂量：Avexitide90mg每日一次（皮下注射）主要终点：2级和3级低血糖复合事件发生率的降低（FDAagreed-upon）预计完成：2026年第一季度完成入组，第三季度公布顶线数据3.5市场机会PBH是一种严重影响生活的疾病，患者常出现疲劳、意识模糊、视力障碍、跌倒、癫痫甚至车祸，并可能导致失业和收入损失。目前美国尚无获批疗法。流行病学数据显示，美国约有16万PBH患者，每年新增减重手术超过20万例，PBH通常在术后1-3年出现。多方医疗索赔数据与文献一致，证实这一患病规模。3.6监管与知识产权FDA突破性疗法认定（用于高胰岛素性低血糖）孤儿药认定（用于高胰岛素性低血糖）专利保护：全球超过200项授权专利，美国专利保护期至2037年，并有资格获得专利期延长4.AMX0035：靶向内质网应激治疗Wolfram综合征Wolfram综合征是一种罕见的致命性单基因遗传病，由WFS1基因突变引起，主要影响多个器官和系统。该病在美国约有3000名患者，目前尚无获批疗法。其典型特征包括：儿童期发病的糖尿病（因胰岛β细胞死亡导致血糖升高）、渐进性视力丧失（视神经细胞死亡所致）、尿崩症（垂体功能异常导致多尿）、听力下降（颅神经损伤）、平衡与协调障碍（小脑受损）、呼吸困难（脑干损伤），最终多数患者在30岁左右死于呼吸衰竭。该病呈进行性发展，需多学科综合管理。4.1药物概述与机制AMX0035是苯丁酸钠和牛磺酸二醇的口服固定剂量复方制剂，旨在通过抑制内质网应激和线粒体功能障碍，减缓神经退行性病变。4.2临床数据：HELIOS试验HELIOS是一项开放标签、单臂2期试验，纳入12例Wolfram综合征患者，治疗长达208周。主要终点为24周时C肽应答（反映胰腺β细胞功能）的变化。24周结果：C肽AUC较基线平均增加，而自然病程中C肽应进行性下降。48周结果：多个疾病相关指标持续稳定或改善，包括胰腺功能、血糖控制、视力及总体症状负担。4.3安全性与耐受性AMX0035总体耐受性良好，最常见不良事件为轻度腹泻（58.3%），无严重不良事件，无因不良事件停药。4.4监管与知识产权FDA孤儿药认定（Wolfram综合征）欧盟孤儿药认定专利：美国专利保护至2040年；正在申请的物质组成专利若获批，可将保护期延长至2043年，有望获得NCE独占期。5.AMX0114：靶向calpain-2的反义寡核苷酸治疗ALS5.1靶点与机制当谷氨酸能、烟碱能或电压门控钙通道过度激活时，会导致细胞外钙离子大量流入细胞内。同时，氧化或缺血应激促使线粒体通过NCX通道释放钙离子，进一步增加胞质内钙浓度。钙超载激活钙蛋白酶-2（Calpain-2），导致神经丝蛋白（NFL）和α-II谱蛋白等细胞骨架蛋白被降解，引发轴突结构不稳定与退化。此过程伴随SBDP-145等特异性片段的产生，是轴突损伤的重要标志物。该机制揭示了ALS早期病理变化的核心通路。AMX0114是一种反义寡核苷酸（ASO），通过特异性敲低calpain-2的mRNA，减少蛋白表达，从而保护轴突。5.2临床前数据在多种神经元损伤模型中，AMX0114显著降低细胞外神经丝轻链（NfL）水平，并在ALS小鼠模型中延长生存期、延迟发病。5.3临床开发：LUMINA试验LUMINA是一项首次人体1期试验，旨在评估AMX0114在ALS患者中的安全性、耐受性和生物活性。试验设计如下：队列1：12例患者，已完成入组，初步数据显示耐受性良好，无治疗相关严重不良事件队列2：12例患者，预计2026年完成入组生物标志物数据：队列1的NfL等数据预计2026年上半年公布5.4监管资格FDA快速通道认定（2025年5月），若后续数据符合标准，有资格获得优先审评。6.AMX0318：新型长效GLP-1受体拮抗剂AMX0318是Amylyx与GubraA/S合作发现的新型长效GLP-1受体拮抗剂，已完成extensive临床前评价。该分子具备：优异的化学稳定性、高溶解度、强效体外活性、体内疗效与耐受性证据符合长效肽类的药代动力学特征。公司已于2026年1月提名AMX0318为开发候选药物，预计2026年启动INDenabling研究，目标2027年提交IND，适应症包括PBH及其他罕见病。7.知识产权分析此外，Avexitide和AMX0035已获得孤儿药认定，享有市场独占期。8.财务状况截至2025年9月30日，Amylyx持有3.44亿美元现金、现金等价物及短期投资，流通股约1.1亿股。公司预计现有资金可支撑运营至2028年，覆盖Avexitide的潜在批准（2027年）及上市初期。9.风险与挑战尽管Amylyx管线充满潜力，但仍需关注以下风险：临床风险：3期LUCIDITY试验结果不及预期；AMX0114早期数据尚未验证疗效。监管风险：FDA对PBH适应症的审评要求可能变化；Wolfram综合征的注册路径尚未明确。竞争风险：PBH领域尚无获批药物，但其他GLP-1相关药物可能在探索中；ALS领域竞争激烈，多家公司布局ASO及小分子。财务风险：公司尚未盈利，研发投入巨大，若Avexitide商业化延迟，可能需额外融资。10.未来展望与总结AmylyxPharmaceuticals凭借其清晰的战略聚焦、差异化的研发管线和经验丰富的团队，正稳步推进多个高潜力项目。核心催化剂包括：2026年Q1，LUCIDITY试验完成入组2026年Q3，LUCIDITY顶线数据公布2026年上半年，AMX0114队列1生物标志数据发布2026年，AMX0114队列2完成入组；AMX0318启动INDenabling研究2027年，若Avexitide获批，预计启动商业化；AMX0318提交IND若Avexitide成功获批，将成为PBH领域首个疗法，迅速占领16万患者市场。同时，AMX0035和AMX0114若验证临床获益，将进一步巩固公司在神经退行性疾病领域的领先地位。