– FDA Advisory Committee voted 7:2 that the available evidence of effectiveness is sufficient to support approval of AMX0035 for the treatment of ALS

– If approved, AMX0035 will be the first treatment in ALS that has demonstrated a significant slowing of disease progression and functional decline, as well as extended survival, in a randomized, placebo-controlled clinical trial, as a standalone therapy or when added to existing approved treatments

– In December 2021, the FDA granted Priority Review and is expected to make a decision on AMX0035 by September 29, 2022, under the Prescription Drug User Fee Act

Amylyx Pharmaceuticals announced that the U.S. Food and Drug Administration’s (FDA) Peripheral and Central Nervous System Drugs Advisory Committee (PCNSDAC) voted (7 yes votes and 2 no votes) that the available evidence of effectiveness is sufficient to support approval of AMX0035 (sodium phenylbutyrate and taurursodiol [also known as ursodoxicoltaurine]) for the treatment of amyotrophic lateral sclerosis (ALS).

The PCNSDAC’s decision was based on a review of all available evidence, including new analyses submitted for discussion at the September 7 meeting and the information presented at the March 30, 2022, PCNS meeting.

“The Committee’s thoughtful review of the data and support of the benefit that AMX0035 may bring to the ALS community, if approved, is promising,” said Jamie Timmons, M.D., Head of Scientific Communications of Amylyx. “The CENTAUR trial data has consistently demonstrated potential benefits of AMX0035 on function and overall survival. We are grateful to the advocacy community, our trial participants and their family members, the ALS clinicians, and countless others who continue to support our mission of ensuring that people living with ALS around the world can access promising new therapies as quickly and efficiently as possible.”

The PCNSDAC recommendations, while not binding, will be considered by the FDA in its review of the pending New Drug Application (NDA) for AMX0035. As previously reported, the Prescription Drug User Fee Act target action date for the NDA is September 29, 2022, which was extended by the FDA to allow more time to review additional analyses of data from the Company’s clinical studies.

About AMX0035

AMX0035 (sodium phenylbutyrate and taurursodiol) is an oral fixed-dose medication with marketing applications pending in the United States and European Union and approved with conditions as ALBRIOZA™ to treat amyotrophic lateral sclerosis (ALS) in Canada. The combination of sodium phenylbutyrate and taurursodiol may reduce neuronal cell death, hypothesized to occur by simultaneously mitigating endoplasmic reticulum (ER) stress and mitochondrial dysfunction. AMX0035 is also being explored for the potential treatment of other neurodegenerative diseases.

About the CENTAUR Trial

CENTAUR was a multicenter Phase 2 clinical trial in 137 participants with ALS encompassing a 6-month randomized placebo-controlled phase and an open-label extension (OLE) long- term follow-up phase. The trial met its primary efficacy endpoint. Administration of AMX0035 (plus standard of care) significantly slowed the rate of functional decline as measured by the Amyotrophic Lateral Sclerosis Functional Rating Scale – Revised (ALSFRS-R) total score compared to placebo (plus standard of care) at the end of the 24-week randomized phase.

CENTAUR results appear to show that AMX0035 was generally well tolerated. Similar rates of adverse events and discontinuations were recorded in the AMX0035 and placebo groups during the 24-week randomized phase. However, gastrointestinal (GI) events occurred with greater frequency (≥2%) in the AMX0035 group. Detailed safety and functional efficacy data from CENTAUR were published in the New England Journal of Medicine. Data from additional analyses from the CENTAUR trial were published in Muscle & Nerve in 2020 and 2022, and the Journal of Neurology, Neurosurgery and Psychiatry in 2022.

About the PHOENIX Trial

The Phase 3 PHOENIX clinical trial (NCT05021536) is a 48-week, randomized placebo- controlled global clinical trial further evaluating the safety and efficacy of AMX0035 (sodium phenylbutyrate and taurursodiol) for the treatment of ALS. The primary efficacy outcome of the trial will be a composite measure of Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) total score progression over 48 weeks and survival over 48 weeks. Secondary endpoints include change in slow vital capacity (SVC), measured both at home using a self-administered spirometer to support virtual data collection and at clinic sites using standard spirometry, quality of life patient-reported outcome assessments, ventilation-free survival rates and other measures. PHOENIX remains underway (recruitment has completed in the U.S. and remains ongoing in Europe) with initial results expected in 2024. More information on the PHOENIX trial can be found at clinicaltrials.gov and eudract.ema.europa.eu.