Phase III Trial of AMX0035 for Amyotrophic Lateral Sclerosis Treatment

Inclusion Criteria:

• Male or female, at least 18 years of age

• Diagnosis of ALS (definite or clinically probable)

• Time since onset of first symptom of ALS should be <24 months prior torandomization;

• If the participant is to be treated with riluzole and/or edaravone during the courseof the trial, then treatment with riluzole and/or edaravone was, at the time of thescreening visit, started and maintained at a stable regimen for at least 14 days forriluzole and/or for a full treatment cycle for edaravone;

• Capable of providing informed consent

• Capable and willing to follow trial procedures including visits to the trial clinicand visit requirements;

• Women of child bearing potential (e.g. not post-menopausal for at least one year orsurgically sterile) must agree to use adequate birth control for the duration of thestudy and 3 months after last dose of study drug. Women must not be planning tobecome pregnant for the duration of the study and 3 months after last dose of studydrug

• Men must agree to practice contraception for the duration of the study and 3 monthsafter last dose of study drug. Men must not plan to father a child or provide forsperm donation for the duration of the study and 3 months after last dose of studydrug

Exclusion Criteria:

• Presence of tracheostomy or permanent assisted ventilation(PAV)

• Slow Vital Capacity (SVC) less than 55%

• History of known allergy to phenyl butyrate or bile salts

• Abnormal liver function defined as bilirubin levels and/or aspartateaminotransferase (AST) and/or alanine aminotransferase (ALT) > 5 times the upperlimit of the normal (obtained within 12 weeks from first dose)

• Renal insufficiency as defined by eGFR <60 mL/min/1.73m^2 (obtained within 12 weeksfrom first dose)

• Pregnant women (confirmed by a pregnancy test within 7 days of first dose) or womencurrently breastfeeding

• Current severe biliary disease which may result in the Investigator medicaljudgement in biliary obstruction including for example active cholecystitis, primarybiliary cirrhosis, sclerosing cholangitis, gallbladder cancer, gangrene of thegallbladder, abscess of the gallbladder

• History of Class III/IV heart failure (per New York Heart Association - NYHA)

• Participant under severe salt restriction where the added salt intake due totreatment would put the participant at risk, in the Investigator clinical judgment

• Presence of unstable psychiatric disease, cognitive impairment, dementia orsubstance abuse that would impair ability of the participant to provide informedconsent, according to Investigator judgment

• Clinically significant unstable medical condition (other than ALS) (e.g.,cardiovascular instability, systemic infection, untreated thyroid dysfunction,severe laboratory test anomaly or clinically significant electrocardiogram [ECG]changes) that would pose a risk to the participant if he/she were to participate inthe trial, according to Investigator judgment

• Previous treatment for ALS with cellular therapies or gene therapies

• Currently enrolled in another trial involving use of an investigational therapy

• Previous treatment with PB or taurursodiol within 30 days from Screening

• Implantation of Diaphragm Pacing System (DPS)

• Currently or previously treated within the last 30 days or planned exposure to anyprohibited medications listed in Section 6.8 of the protocol