Amylyx Pharmaceuticals, Inc. Annual Report - Fiscal Year Ended December 31, 2025

This report offers an in-depth look at Amylyx Pharmaceuticals' performance and strategic direction for the fiscal year ending December 31, 2025. This period proved pivotal as the company executed a significant strategic shift, moving past its initial commercial success to concentrate on a revitalized pipeline.

Business Overview Amylyx Pharmaceuticals, a biopharmaceutical company based in Cambridge, Massachusetts, focuses on developing treatments for serious diseases. Its stock trades on the Nasdaq Global Select Stock Market under the ticker symbol AMLX. While no longer a startup, Amylyx operates as a "smaller reporting company," indicating its continued growth and evolution.

The most significant event impacting Amylyx in late 2024 and early 2025 was the voluntary withdrawal of Relyvrio (AMX0035) from the market for Amyotrophic Lateral Sclerosis (ALS). This decision followed the Phase 3 PHOENIX trial, which failed to meet its primary or secondary goals, showing no statistically significant benefit for ALS patients. This outcome marked a critical turning point, prompting Amylyx to pivot its primary focus.

After the withdrawal, Amylyx strategically acquired assets related to Avexitide from Eiger BioPharmaceuticals Inc. in July 2024. Avexitide, now the company's leading clinical candidate, targets post-bariatric hypoglycemia (PBH), a serious complication following weight-loss surgery. The ongoing Phase 3 LUCIDITY trial for Avexitide represents the company's most advanced clinical program.

Other key pipeline programs include:

• AMX0035: Still under investigation for Wolfram syndrome, a rare genetic disorder.
• AMX0114: In a Phase 1 clinical trial (LUMINA trial) for ALS, exploring a new approach to this devastating neurological disease.
• AMX0318: In earlier, preclinical research stages, also targeting PBH.

Financial Performance for Fiscal Year 2025 The withdrawal of Relyvrio significantly impacted Amylyx's financial results for 2025.

• Revenue: Amylyx reported approximately $8.5 million in total revenue for the fiscal year. This figure primarily came from residual product sales and other minor income streams after the Relyvrio withdrawal. It marks a substantial decrease from previous years when Relyvrio was commercially available, reflecting the halt of significant commercial sales.
• Net Loss: The company reported a net loss of approximately $285 million. This loss primarily resulted from ongoing significant research and development (R&D) expenses for its pipeline, general and administrative (G&A) costs related to operations and restructuring, and the absence of substantial product sales revenue.
• Operating Expenses: Research and development expenses remained a primary driver of spending, supporting the advancement of Avexitide and other pipeline candidates. Restructuring efforts, including severance costs, impacted selling, general, and administrative expenses, which also cover ongoing corporate overhead.
• Earnings Per Share (EPS): The net loss resulted in a basic and diluted loss per share, consistent with the company's pre-commercial stage for its current lead assets.

Key Developments and Operational Highlights

• Relyvrio Withdrawal & Restructuring: The decision to withdraw Relyvrio in early 2025 prompted a comprehensive Restructuring Plan, which Amylyx implemented in April 2024 (anticipating the PHOENIX trial results and potential withdrawal). This plan included significant cost-cutting, workforce reductions, and a strategic reallocation of resources to focus on the remaining pipeline, especially Avexitide. The restructuring aimed to extend the company's cash runway and prioritize its most promising assets.
• Avexitide Acquisition and Advancement: Acquiring Avexitide assets from Eiger BioPharmaceuticals Inc. in July 2024 marked a crucial strategic move, giving Amylyx a new lead candidate. The ongoing Phase 3 LUCIDITY trial for Avexitide in PBH expects topline data in late 2026 or early 2027, representing the company's next major value inflection point.
• Pipeline Progression: Despite these challenges, Amylyx continued advancing its other clinical programs, including the Phase 1 LUMINA trial for AMX0114 in ALS. This demonstrates the company's commitment to addressing unmet medical needs.

Financial Health

• Cash Position: As of December 31, 2025, Amylyx held approximately $310 million in cash, cash equivalents, and marketable securities. Two "Underwritten Public Offerings" in January and September 2025 bolstered this cash position, raising a combined net total of approximately $200 million. While common for biotech companies seeking R&D capital, these offerings involved selling new shares to investors, which dilutes existing shareholders.
• Liquidity and Capital Resources: The company's current cash and equivalents provide enough liquidity to fund operations and pipeline development for a projected period, extended by the restructuring plan. However, with significant R&D expenditures and limited product revenue, Amylyx anticipates needing additional capital to complete clinical trials, seek regulatory approvals, and commercialize any future products.
• Debt: Amylyx primarily relies on equity financing to fund its operations.
• Market Valuation: As of June 30, 2025, Amylyx's publicly traded shares had a total market value of around $518.2 million. The company had approximately 110.5 million shares of common stock outstanding as of February 23, 2026.

Future Outlook and Strategy Amylyx's future strategy centers on advancing Avexitide through its Phase 3 trial and pursuing regulatory approval for PBH. Amylyx also aims to continue developing its other pipeline assets, including AMX0035 for Wolfram syndrome and AMX0114 for ALS. Management focuses on disciplined capital allocation to extend the cash runway and maximize the value of the remaining pipeline. For future product launches, Amylyx plans to either build its own commercial infrastructure or seek strategic partnerships, depending on the asset and market opportunity. With operations in Canada, Switzerland, Netherlands, UK, Germany, and various US states, the company maintains a global footprint, positioning it for potential international expansion if its pipeline succeeds. Regulatory developments and the competitive landscape will continue to be critical factors shaping its path forward.

Competitive Position The therapeutic areas Amylyx targets are highly competitive, with numerous established pharmaceutical companies and emerging biotechs developing similar or alternative treatments.

• Post-Bariatric Hypoglycemia (PBH): For Avexitide, the company faces competition from other investigational therapies in various stages of clinical development, as well as off-label use of existing drugs and dietary management strategies. Key competitive factors include mechanism of action, efficacy, safety profile, route of administration, and intellectual property protection.
• Amyotrophic Lateral Sclerosis (ALS): For AMX0114, the ALS market is characterized by significant unmet need and ongoing research. Competitors include companies developing small molecules, biologics, and gene therapies, each with different mechanisms of action aimed at slowing disease progression or managing symptoms.
• Wolfram Syndrome: For AMX0035 in Wolfram syndrome, the competitive landscape is less crowded due to the ultra-rare nature of the disease, but any potential therapy would still need to demonstrate significant clinical benefit to gain market acceptance.

Amylyx's ability to compete effectively will depend on the clinical success of its pipeline candidates, its intellectual property portfolio, its capacity to navigate regulatory pathways, and its ability to commercialize products efficiently.

Risk Factors Investing in Amylyx Pharmaceuticals carries significant risks, particularly given its current transitional phase:

• Clinical Trial Success: The success of Avexitide's LUCIDITY trial is paramount. There is no guarantee that the trial will meet its endpoints, or that any other pipeline candidates will successfully complete clinical development.
• Regulatory Approval: Even with positive trial results, obtaining regulatory approval from agencies like the FDA remains a complex, lengthy, and uncertain process.
• Commercialization Challenges: If approved, successfully launching and commercializing Avexitide or other drugs will require significant investment in sales, marketing, and market access, and will face intense competition.
• Funding Needs: Amylyx continues to operate at a significant net loss, requiring substantial additional funding to complete clinical trials, seek approvals, and commercialize products. There is no guarantee that future financing will be available on favorable terms or at all, potentially leading to dilution for existing shareholders or a curtailment of development programs.
• Competition: The therapeutic areas Amylyx targets are highly competitive, with other companies developing similar or alternative treatments.
• Intellectual Property: Protecting the company's intellectual property is crucial, and it faces risks from patent challenges or infringement.
• Reliance on Key Personnel: The company's success depends on its ability to retain key scientific and management personnel.
• Product Liability: As a biopharmaceutical company, Amylyx faces inherent risks of product liability claims, which could be costly and divert management's attention.
• Manufacturing and Supply Chain: The company relies on third parties to manufacture its clinical and potential commercial products, posing risks related to quality, cost, and timely supply.