FDA label 8c5790a5-b2c7-4cab-9be9-bbca37b3f21d

5 WARNINGS AND PRECAUTIONS Risk in Patients with Enterohepatic Circulation Disorders, Pancreatic Disorders, or Intestinal Disorders: In patients with disorders that interfere with bile acid circulation, consider consulting with a specialist. Monitor for new or worsening diarrhea in these patients. These conditions may also lead to decreased absorption of either of the components of RELYVRIO. ( 5.1 ) Use in Patients Sensitive to High Sodium Intake: RELYVRIO has a high sodium content. In patients sensitive to salt intake, consider the amount of daily sodium intake in each dose of RELYVRIO and monitor appropriately. ( 5.2 ) 5.1 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, etc.), severe pancreatic disorders (e.g., pancreatitis), and intestinal disorders that may alter concentrations of bile acids (e.g., ileal resection, regional ileitis, etc.) were excluded from the study, therefore there is no clinical experience in these conditions. 5.2 Use in Patients Sensitive to High Sodium Intake RELYVRIO has a high salt content. Each initial daily dosage of one packet contains 464 mg of sodium; each maintenance dosage of two 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.

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Risk in Patients with Enterohepatic Circulation Disorders, Pancreatic Disorders, or Intestinal Disorders [see Warnings and Precautions ( 5.1 )] Use in Patients Sensitive to High Sodium Intake [see Warnings and Precautions ( 5.2 )] Most common adverse reactions (at least 15% and at least 5% greater than placebo) are diarrhea, abdominal pain, nausea, and upper respiratory tract infection. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Amylyx Pharmaceuticals, Inc. at 877-374-1208 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of RELYVRIO was evaluated in Study 1 which enrolled 137 adult patients with ALS randomized (2:1) to RELYVRIO (n = 89) or placebo (n = 48) for 24 weeks. In Study 1, there were 5 (6%) RELYVRIO-treated patients and 2 (4%) placebo patients who died during the 24-week study. The deaths appeared to be related to ALS disease progression. 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. Table 1 lists the common adverse reactions that occurred in more than 5% of patients taking RELYVRIO and were at least 5% greater than in patients taking placebo in Study 1. Table 1: Adverse Reactions Reported in More than 5% of RELYVRIO-Treated Patients with ALS and at least 5% Greater than Placebo (Study 1) Adverse Reaction RELYVRIO (N = 89) % Placebo (N = 48) % Diarrhea * 25 19 Abdominal pain * 21 13 Nausea 18 13 Upper respiratory tract infection * 18 10 Fatigue * 12 6 Salivary hypersecretion 11 2 Dizziness 10 4 *Adverse reaction is composed of several similar terms.

<table width="508px"><caption>Table 1: Adverse Reactions Reported in More than 5% of RELYVRIO-Treated Patients with ALS and at least 5% Greater than Placebo (Study 1)</caption><col/><col/><col/><tbody><tr><td valign="bottom" styleCode=" Botrule Toprule"><content styleCode="bold">Adverse Reaction</content></td><td align="center" styleCode=" Botrule Toprule"> <paragraph><content styleCode="bold">RELYVRIO </content> <content styleCode="bold">(N = 89) </content><content styleCode="bold">%</content></paragraph></td><td align="center" styleCode=" Botrule Toprule"> <paragraph><content styleCode="bold">Placebo (N = 48) </content><content styleCode="bold">%</content></paragraph></td></tr><tr><td>Diarrhea^*</td><td align="center">25</td><td align="center"> 19</td></tr><tr><td>Abdominal pain^*</td><td align="center">21</td><td align="center"> 13</td></tr><tr><td>Nausea</td><td align="center">18</td><td align="center">13</td></tr><tr><td>Upper respiratory tract infection^* </td><td align="center">18</td><td align="center"> 10</td></tr><tr><td>Fatigue^* </td><td align="center"> 12</td><td align="center"> 6</td></tr><tr><td>Salivary hypersecretion </td><td align="center">11</td><td align="center">2</td></tr><tr><td styleCode=" Botrule">Dizziness </td><td align="center" styleCode=" Botrule"> 10</td><td align="center" styleCode=" Botrule"> 4</td></tr><tr><td valign="top" colspan="3" styleCode=" Toprule"><paragraph>*Adverse reaction is composed of several similar terms.</paragraph></td></tr></tbody></table>