Amylyx Pharmaceuticals, Inc. (NASDAQ: AMLX) (“Amylyx” or the “Company”) today announced an update on the ongoing review of its Marketing Authorisation Application (MAA) for AMX0035 (sodium phenylbutyrate and ursodoxicoltaurine [also known as taurursodiol]) for the treatment of adults with amyotrophic lateral sclerosis (ALS) by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA). Following an oral explanation held at the May meeting of the CHMP, Amylyx was informed that the CHMP is trending toward a negative opinion on the application for conditional marketing authorisation of AMX0035.

“We disagree with the current view expressed by the CHMP and remain confident in the data from the CENTAUR trial. Should a negative opinion ultimately be issued, we intend to request a formal re-examination procedure,” said Tammy Sarnelli, Global Head, Regulatory Affairs and Clinical Compliance at Amylyx.

The CHMP is expected to adopt a formal opinion on the MAA at its next meeting, which will be held June 19-22, 2023. If a negative opinion is received in June, the Company intends to request a formal re-examination of the opinion, which is an approximately four-month process.

The MAA for AMX0035 is based on data from the CENTAUR clinical trial, a randomized, multicenter, placebo-controlled trial in participants with ALS (n=137), which were the basis of the full approval received from the U.S. Food and Drug Administration (FDA) and approval with conditions by Health Canada. The trial met its prespecified primary outcome and AMX0035 is the first ALS therapy to demonstrate, in the same trial, both a statistically significant benefit in function, as well as an observed benefit on survival in a longer-term post hoc analysis. The CENTAUR data were published in the peer-reviewed medical journals the New England Journal of Medicine, Muscle & Nerve, and the Journal of Neurology, Neurosurgery, and Psychiatry. AMX0035 demonstrated a generally well-tolerated safety profile in the CENTAUR trial, with similar reported rates of adverse events and discontinuations in AMX0035 and placebo groups during the 24-week randomized phase; however, gastrointestinal events occurred with greater frequency (≥2%) in the AMX0035 group.

ALS affects approximately 29,000 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). In the first six months following FDA approval in the U.S., as of March 31, 2023, there were roughly 3,000 people actively taking RELYVRIO^® in the U.S.

“There has not been a new product approved in the European Union for ALS in over 25 years. We know from the European ALS community that there is a desperate need for new therapeutic options for this devastating disease, and timely access to safe and effective treatments is especially important. While our MAA is under review, we remain committed to exploring all potential paths forward given people living with ALS have no time to wait,” said Stéphanie Hoffmann-Gendebien, Head, General Manager – International Markets, EMEA at Amylyx.

About RELYVRIO^®/ALBRIOZA™/AMX0035

RELYVRIO^®, 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. Additionally, the European Medicines Agency (EMA) is reviewing the Company’s Marketing Authorisation Application for AMX0035 for the treatment of ALS in Europe and recently informed the Company that the CHMP is trending toward a negative opinion on the AMX0035 application. AMX0035 is being explored for the potential treatment of 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 ALS

ALS 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 approximately 29,000 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 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 and EMEA. For more information, visit amylyx.com and follow us on LinkedIn and Twitter. 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, statements regarding re-examination and other potential options if CHMP issues a negative opinion for AMX0035; the approvability of AMX0035 for conditional marketing authorisation; the ability to provide post-authorisation confirmatory data; our plans to make AMX0035 available in Europe; the ongoing commercialization of RELYVRIO and ALBRIOZA; the potential continued market acceptance and market opportunity for RELYVRIO and ALBRIOZA; the potential of AMX0035 as a treatment for ALS and the Company’s plans to explore the use of AMX0035 for other neurodegenerative diseases; and expectations regarding our longer-term strategy. Any forward-looking statements in this press release 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: Amylyx’ ability to fund operations, the success, cost, and timing of Amylyx’ program development activities, Amylyx’ ability to execute on its commercial and regulatory strategy, regulatory developments, expectations regarding the timing and outcome of EMA’s review of AMX0035 for the treatment of ALS, Amylyx’ reliance on third parties, including to conduct clinical trials and manufacture products, and the effect of global economic uncertainty and financial market volatility caused by economic effects of rising inflation and interest rates, the COVID-19 pandemic, geopolitical instability, changes in international trade relationships and military conflicts, as well as the risks and uncertainties set forth in Amylyx’ United States Securities and Exchange Commission (SEC) filings, including Amylyx’ Quarterly Report on Form 10-Q for the quarter ended March 31, 2023, and subsequent filings with the SEC. All forward-looking statements contained in this press release speak only as of the date on which they were made. Subject to any obligations under applicable law, 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.

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There has not been a new product approved in the European Union for ALS in over 25 years. While our MAA is under review, we remain committed to exploring all potential paths forward given people living with ALS have no time to wait.