Amylyx Pharmaceuticals is a biopharmaceutical company committed to developing novel treatments for devastating neurodegenerative diseases and endocrine conditions. Founded in 2013, the company has built a diverse pipeline of product candidates targeting areas with significant unmet medical needs. With a focus on innovative science and a patient-centric approach, Amylyx is poised to make a meaningful impact in the lives of those affected by these debilitating disorders.
Business Overview and History
Amylyx was founded in 2013 with the mission of developing new treatments for people living with serious and fatal neurodegenerative diseases and endocrine conditions. The company's initial focus was on addressing unmet needs in the field of neurodegenerative diseases, an area that had seen very limited success in product development historically.
In 2016, Amylyx began researching and developing AMX0035, a combination therapy designed to target two key pathways implicated in neurodegeneration - endoplasmic reticulum stress and mitochondrial dysfunction. Over the next several years, the company conducted preclinical studies and clinical trials evaluating AMX0035 in conditions such as amyotrophic lateral sclerosis (ALS) and Alzheimer's disease.
In 2022, Amylyx received regulatory approval for AMX0035, known as RELYVRIO in the U.S. and ALBRIOZA in Canada, for the treatment of ALS. This represented the company's first commercial product and its first major milestone. However, in 2024, Amylyx announced it would be voluntarily discontinuing the marketing authorizations for RELYVRIO/ALBRIOZA and removing the product from the market based on topline results from a Phase 3 clinical trial that did not meet its primary and secondary endpoints.
Despite this setback, Amylyx remained undeterred in its mission to develop transformative therapies. In July 2024, the company completed the acquisition of avexitide, an investigational, first-in-class glucagon-like peptide-1 (GLP-1) receptor antagonist, for the potential treatment of hyperinsulinemic hypoglycemia, including post-bariatric hypoglycemia (PBH) and congenital hyperinsulinism (HI).
Avexitide has received Breakthrough Therapy Designation from the FDA for both PBH and congenital HI, as well as Orphan Drug Designation for the treatment of hyperinsulinemic hypoglycemia. Amylyx is on track to initiate a Phase 3 clinical trial for avexitide in PBH in the first quarter of 2025, with topline data expected in 2026.
In addition to avexitide, Amylyx's pipeline includes AMX0035 for the treatment of Wolfram syndrome and progressive supranuclear palsy (PSP), as well as AMX0114, an antisense oligonucleotide targeting calpain-2 for the treatment of ALS. The company recently reported positive topline data from the Phase 2 HELIOS trial of AMX0035 in Wolfram syndrome, demonstrating improvements or stabilization across multiple disease measures at 24 weeks, with sustained improvements observed in longer-term data.
Amylyx's focus on addressing high unmet needs is further evidenced by the Orphan Drug Designations granted to AMX0035 for the treatment of Wolfram syndrome and to avexitide for the treatment of hyperinsulinemic hypoglycemia, including PBH and congenital HI.
Financial Snapshot
As of September 30, 2024, Amylyx reported $234.4 million in cash, cash equivalents, and marketable securities, providing a strong financial foundation to advance its pipeline. The company's net product revenue for the third quarter of 2024 was $0.4 million, primarily related to true-ups and trailing rebates from the discontinued sales of RELYVRIO and ALBRIOZA (the Canadian brand name for AMX0035). This represents a significant decrease from the $102.69 million in product revenue reported in the same period in 2023, which was primarily related to sales of RELYVRIO in the U.S. and ALBRIOZA in Canada before their discontinuation.
Research and development expenses for the third quarter of 2024 were $21.2 million, down from $30.0 million in the same period of 2023, reflecting a decrease in clinical expenses following the PHOENIX trial results and a reduction in payroll and personnel-related costs due to the company's restructuring efforts. Selling, general, and administrative expenses also decreased significantly, from $48.7 million in the third quarter of 2023 to $17.8 million in the third quarter of 2024, driven by the decline in payroll, personnel-related costs, and consulting and professional services.
During the third quarter of 2024, Amylyx recorded a net loss of $72.7 million, or $1.07 per share. This is in contrast to the company's performance in the most recent fiscal year (2023), where it reported revenue of $380.79 million and net income of $49.27 million. The company's cash runway is expected to extend into 2026, providing the necessary resources to execute on its key pipeline milestones.
On July 9, 2024, Amylyx completed the acquisition of substantially all the assets and interests in the development, manufacture, and commercialization of avexitide from Eiger BioPharmaceuticals, Inc. As a result, during the third quarter of 2024, Amylyx recorded a charge of approximately $36.2 million associated with the acquired in-process research and development (IPR&D) assets of avexitide with no alternative future use.
Liquidity
Amylyx's strong cash position of $234.4 million as of September 30, 2024, provides the company with sufficient liquidity to fund its operations and advance its pipeline through key milestones. The expected cash runway into 2026 demonstrates the company's prudent financial management and strategic allocation of resources. This liquidity position allows Amylyx to focus on executing its clinical development plans without immediate financing concerns, particularly important given the company's diverse pipeline and ongoing clinical trials.
The company's debt-to-equity ratio stood at 0.013 as of September 30, 2024, indicating a low level of leverage. Both the current ratio and quick ratio were 4.55, suggesting strong short-term liquidity and the ability to meet current obligations.
Operational Highlights and Upcoming Milestones
Avexitide for Post-Bariatric Hypoglycemia (PBH) - Amylyx is on track to initiate a Phase 3 clinical trial for avexitide in PBH in the first quarter of 2025, with topline data expected in 2026. - The Phase 2 and Phase 2b studies of avexitide in PBH demonstrated statistically significant and clinically meaningful reductions in both Level 2 and Level 3 hypoglycemia events, with the 90 mg dose showing a 66% reduction in Level 3 events and a 53% reduction in Level 2 events. - The primary efficacy outcome for the upcoming Phase 3 trial will be the reduction in the composite of Level 2 and Level 3 hypoglycemia events. Amylyx plans to share the full trial design prior to initiating the study.
AMX0035 for Wolfram Syndrome - In October 2024, the company reported positive topline data from the Phase 2 HELIOS trial of AMX0035 in Wolfram syndrome, with improvements or stabilization observed across multiple disease measures at 24 weeks and sustained improvements in longer-term data. - The data showed improvement in pancreatic function as measured by the primary endpoint of C-peptide response at 24 weeks, as well as similar overall improvements or stabilization across all secondary endpoints. - Amylyx plans to meet with the FDA and other stakeholders to inform the design of a Phase 3 clinical trial for AMX0035 in Wolfram syndrome, with an update expected in 2025.
AMX0035 for Progressive Supranuclear Palsy (PSP) - The ongoing Phase 2b/3 ORION trial of AMX0035 in PSP is recruiting well, and the company expects to report data from an interim analysis in mid-2025. - The interim analysis will inform a go/no-go decision on this program. - The rationale for the ORION trial is based on the significant reductions in total tau and phospho-tau 181 observed in a prior Phase 2 trial of AMX0035 in Alzheimer's disease.
AMX0114 for Amyotrophic Lateral Sclerosis (ALS) - Amylyx received clearance from Health Canada for the clinical trial application for AMX0114, an antisense oligonucleotide targeting calpain-2, in people living with ALS. - The company plans to initiate a Phase 1 multiple ascending dose, placebo-controlled trial called LUMINA in Canada by the end of 2024 or in early 2025, with early cohort data expected in 2025.
Risks and Challenges
Despite the progress made by Amylyx, the company faces several risks and challenges that investors should be aware of:
1. Regulatory Uncertainty: The success of Amylyx's pipeline candidates, including avexitide and AMX0035 for additional indications, is contingent upon obtaining regulatory approvals. Delays or failures in the regulatory process could significantly impact the company's growth.
2. Clinical Development Risks: The company's clinical trials for AMX0035, avexitide, and AMX0114 may encounter setbacks, such as enrollment challenges, safety concerns, or failure to demonstrate clinically meaningful efficacy. Any negative results could adversely affect the company's prospects.
3. Competition and Market Acceptance: Amylyx operates in highly competitive therapeutic areas, and its product candidates may face competition from other treatments or face challenges in gaining market acceptance, even if approved.
4. Reliance on Third Parties: Amylyx relies on third-party manufacturers, suppliers, and collaborators, and any disruptions in these relationships or their inability to perform could impact the company's operations and development timelines.
5. Financing and Cash Management: While Amylyx currently has a strong cash position, its future capital requirements may exceed its available resources, requiring the company to seek additional financing, which may not be available on favorable terms or at all.
6. Legal Challenges: In February 2024, a putative class action lawsuit was filed against the company and certain current and former officers alleging false and misleading statements related to the commercial results and prospects for RELYVRIO. Additionally, in October 2024, a derivative complaint was filed against certain current and former director and officer defendants, alleging violations of securities laws, breach of fiduciary duty, insider trading, and unjust enrichment. These legal challenges could result in significant costs and divert management's attention from core business operations.
7. Product Discontinuation Impact: The voluntary discontinuation of RELYVRIO/ALBRIOZA in April 2024 has significantly impacted the company's revenue stream, as evidenced by the sharp decline in product revenue from $102.69 million in Q3 2023 to $416,000 in Q3 2024. This loss of revenue puts additional pressure on the company to successfully develop and commercialize its pipeline candidates.
Conclusion
Amylyx Pharmaceuticals is a biopharmaceutical company with a patient-centric approach, working to address high unmet needs in neurodegenerative diseases and endocrine conditions. Despite the setback with RELYVRIO, the company has remained focused on advancing its diverse pipeline, highlighted by the promising data for avexitide in PBH and AMX0035 in Wolfram syndrome. With a strong cash position and a clear strategic vision, Amylyx is well-positioned to continue its mission of developing transformative therapies for those affected by these devastating disorders. The company's ability to navigate the challenges ahead, including the ongoing clinical trials and regulatory processes, will be crucial in determining its long-term success and potential to deliver value to patients and shareholders alike.