Business Overview and History
Amylyx Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company dedicated to developing novel therapies for communities with high unmet medical needs. The company's diverse pipeline targets both neurodegenerative diseases and endocrine conditions, showcasing its commitment to addressing a wide range of debilitating illnesses.
Amylyx was founded in 2015 with the goal of discovering and advancing transformative treatments. The company's initial focus was on neurodegenerative diseases, a field that has historically seen limited success in product development. In 2022, Amylyx achieved a significant milestone when its lead product candidate, AMX0035, received marketing authorization in Canada under the brand name ALBRIOZA for the treatment of amyotrophic lateral sclerosis (ALS). Later that same year, AMX0035 was also approved in the United States under the brand name RELYVRIO for the treatment of ALS, marking the company's first commercial product.
However, Amylyx faced a major setback in 2024 when the global Phase 3 PHOENIX clinical trial for RELYVRIO/ALBRIOZA failed to meet its primary and secondary endpoints. As a result, the company made the difficult decision to voluntarily discontinue the marketing authorizations for RELYVRIO/ALBRIOZA and remove the product from the market in the U.S. and Canada. Despite this challenge, Amylyx remained committed to advancing its pipeline of product candidates.
In 2024, Amylyx expanded its portfolio by acquiring the rights to avexitide, an investigational GLP-1 receptor antagonist, through the acquisition of assets from Eiger Biopharmaceuticals. Avexitide had previously been evaluated in multiple Phase 2 clinical studies for the treatment of post-bariatric hypoglycemia and congenital hyperinsulinism.
One of Amylyx's key assets is avexitide, an investigational first-in-class glucagon-like peptide-1 (GLP-1) receptor antagonist. Avexitide is being evaluated for the treatment of post-bariatric hypoglycemia (PBH), a debilitating condition that affects an estimated 160,000 people in the U.S. and has no approved treatments. The company recently announced the initiation of the pivotal Phase 3 LUCIDITY trial for avexitide in PBH, with topline data anticipated in the first half of 2026.
In addition to avexitide, Amylyx is advancing AMX0035, a combination therapy targeting endoplasmic reticulum (ER) stress and mitochondrial dysfunction, in Wolfram syndrome and progressive supranuclear palsy (PSP). Wolfram syndrome is a rare, fatal, monogenic, progressive disease affecting an estimated 3,000 people in the U.S., while PSP is a rare, progressive, and fatal neurodegenerative disorder estimated to impact 23,000 individuals in the U.S.
Amylyx's pipeline also includes AMX0114, an antisense oligonucleotide targeting calpain-2 for the treatment of amyotrophic lateral sclerosis (ALS). The company recently announced the lifting of the clinical hold on the Phase 1 LUMINA trial of AMX0114 and is working to open U.S. sites for the study.
Financials and Liquidity
As of December 31, 2024, Amylyx reported cash, cash equivalents, and marketable securities of $176.5 million. In January 2025, the company raised an additional $65.5 million through a public offering, extending its cash runway through the end of 2026.
For the full year 2024, Amylyx reported total revenue of $87.37 million, down from $380.79 million in 2023, primarily due to the voluntary discontinuation of sales of its only approved product, RELYVRIO/ALBRIOZA, in the U.S. and Canada. The company's net loss for 2024 was $301.74 million, compared to net income of $49.27 million in 2023. The discontinuation of RELYVRIO/ALBRIOZA resulted in $118.68 million in inventory impairment and loss on purchase commitments.
Amylyx's operating cash flow for 2024 was negative $167.65 million, while free cash flow was negative $167.80 million. The company's current ratio, a measure of its short-term liquidity, stood at 6.668 as of December 31, 2024, indicating a strong ability to meet its near-term obligations. The company's debt-to-equity ratio was 0.012, suggesting a low level of financial leverage.
Research and development expenses were $104.1 million in 2024, down from $128.2 million in 2023, primarily due to decreased spending on AMX0035 for ALS after the PHOENIX trial failed to meet its endpoints. Selling, general and administrative expenses were $114.3 million in 2024, down from $188.4 million in 2023, following the company's restructuring plan implemented in April 2024.
The discontinuation of RELYVRIO/ALBRIOZA in April 2023 resulted in $31 million in cash used for product returns, rebates, and settlements of previous purchase commitments.
Key Developments and Upcoming Milestones
In April 2024, Amylyx announced a restructuring plan to focus its resources on key clinical and preclinical programs, which included a 70% reduction in its workforce. This move was aimed at streamlining the company's operations and aligning its efforts with its core development activities.
The company's upcoming milestones include:
1. Completion of recruitment and top-line data from the pivotal Phase 3 LUCIDITY trial of avexitide in PBH, expected in the first half of 2026. Enrollment is expected to be completed by the end of 2025. 2. Week 48 data from the ongoing Phase 2 HELIOS trial of AMX0035 in Wolfram syndrome, expected in the coming months, which will inform the design of a potential Phase 3 trial. 3. Unblinded interim analysis of the Phase 2b portion of the ORION trial evaluating AMX0035 in PSP, expected in the third quarter of 2025. 4. Early cohort data from the Phase 1 LUMINA trial of AMX0114 in ALS, expected in 2025.
Risks and Challenges
Amylyx faces several risks and challenges common to the biopharmaceutical industry, including the inherent uncertainty of clinical development, regulatory approvals, and commercialization. The company's heavy reliance on the success of its lead programs, avexitide and AMX0035, poses a significant risk, as any setbacks in these programs could have a material impact on the company's overall prospects.
Additionally, Amylyx may face competition from other therapies in development for the indications it is targeting, which could impact the commercial potential of its product candidates. The company's ability to secure adequate funding to support its R&D efforts and operational expenses is also a key risk factor.
Conclusion
Amylyx Pharmaceuticals is a promising clinical-stage biopharmaceutical company with a diversified pipeline addressing high unmet needs in both neurodegenerative diseases and endocrine conditions. The company's lead programs, avexitide and AMX0035, have demonstrated encouraging results in early-stage trials and are progressing through late-stage development.
Despite the risks and challenges inherent to the industry, Amylyx's focus on executing its clinical development strategy, building a strong commercial infrastructure, and securing necessary funding positions the company well to potentially bring much-needed treatments to patients in the years ahead. As the company navigates the critical milestones ahead, investors will closely monitor its ability to deliver on its promising pipeline and drive long-term value.