HEALEY ALS Platform Trial - Master Protocol

Inclusion Criteria:

1. Sporadic or familial ALS diagnosed as clinically possible, probable, lab-supportedprobable, or definite ALS defined by revised El Escorial criteria.

2. Age 18 years or older.

3. Capable of providing informed consent and complying with study procedures, in theSI's opinion.

4. Time since onset of weakness due to ALS ≤ 24 months at the time of the MasterProtocol Screening Visit.

5. Vital Capacity ≥ 50% of predicted capacity at the time of the Master ProtocolScreening Visit measured by Slow Vital Capacity (SVC), or, if required due topandemic-related restrictions, Forced Vital Capacity (FVC) measured in person.

6. Participants must either not take riluzole or be on a stable dose of riluzole for ≥ 30 days prior to the Master Protocol Screening Visit.

7. Participants must either not take edaravone or have completed at least one cycle (typically 14 days) of edaravone prior to the Master Protocol Screening Visit.

8. Participants must have the ability to swallow pills and liquids at the time of theMaster Protocol Screening Visit and, in the SI's opinion, have the ability toswallow for the duration of the study.

9. Geographically accessible to the site.

Exclusion Criteria:

1. Clinically significant unstable medical condition (other than ALS) that would pose arisk to the participant, according to SI's judgment (e.g., cardiovascularinstability, systemic infection), or clinically significant laboratory abnormalityor EKG changes. Clinically significant abnormal liver or kidney function isexclusionary. The following values [alanine aminotransferase (ALT) or aspartateaminotransferase (AST) > 3 times the upper limit of normal (ULN) or estimatedGlomerular Filtration Rate (eGFR) < 30 mL/min/1.73m2] are exclusionary regardless ofclinical symptoms.

2. Presence of unstable psychiatric disease, cognitive impairment, dementia orsubstance abuse that would impair ability of the participant to provide informedconsent, in the SI's opinion.

3. Active cancer or history of cancer, except for the following: basal cell carcinomaor successfully treated squamous cell carcinoma of the skin, cervical carcinoma insitu, prostatic carcinoma in situ, or other malignancies curatively treated and withno evidence of disease recurrence for at least 3 years.

4. Use of investigational treatments for ALS (off-label use or active participation ina clinical trial) within 5 half-lives (if known) or 30 days (whichever is longer)prior to the Master Protocol Screening Visit.

5. Exposure at any time to any gene therapies under investigation for the treatment ofALS (off-label use or investigational).

6. If female, breastfeeding, known to be pregnant, planning to become pregnant duringthe study, or of child-bearing potential and unwilling to use effectivecontraception, for the duration of the trial and for 3 months, or as specified ineach RSA, after discontinuing study treatment.

7. If male of reproductive capacity, unwilling to use effective contraception for theduration of the trial and for 3 months, or as specified in each RSA, afterdiscontinuing study treatment.

8. Anything that would place the participant at increased risk or preclude theparticipant's full compliance with or completion of the study, in the SI's opinion.

9. If a participant is being re-screened, the disqualifying condition has not beenresolved, or the mandatory wash-out duration has not occurred.