A Clinical Trial to Evaluate NB-4746 in Participants With Amyotrophic Lateral Sclerosis.

Inclusion Criteria:

• ALS Criteria for Phase 1b:

1. Participants in Phase 1b must have:

2. Diagnosis of ALS per Gold Coast Criteria; and

3. Symptom onset ≤48 months prior to randomization on Day 1. Date of first ALSsymptom (any ALS symptom) onset is defined as the onset of weakness in thelimbs, bulbar region, or trunk. Weakness in the bulbar region includesdysarthria and dysphagia.

• ALS Criteria for Phase 2:

2. Participants in Phase 2 must have:

3. Diagnosis of ALS per Gold Coast Criteria; and

4. Symptom onset ≤24 months prior to randomization on Day 1. Date of first ALSsymptom (any ALS symptom) onset is defined as the onset of weakness in thelimbs, bulbar region, or trunk. Weakness in the bulbar region includesdysarthria and dysphagia.

• Additional Inclusion Criteria (All Participants):

• Male or female participants aged ≥18 years and ≤80 years at the time of signinginformed consent.

• Score of at least 2 on the swallowing function of the ALSFRS-R.

• Slow vital capacity (SVC) ≥60% of predicted at Screening.

• If taking riluzole, participant must be on a stable dose for ≥60 days prior to Day

• If taking edaravone, participant must have completed at least 1 cycle of edaravoneprior to Day 1.

• Screening laboratory test values within normal ranges. If taking riluzole,participant must be on a stable dose for ≥60 days prior to Screening lab bloodsample. If taking edaravone, participant must have completed at least 1 cycle ofedaravone prior to the Screening lab sample.

• Willing to adhere to contraceptive requirements during the study period as describedin Appendix 1.

• Capable of giving signed informed consent, as described in Section 13.2.2, whichincludes compliance with the requirements and restrictions listed in the ICF and inthis protocol.

Exclusion Criteria:

• Presence of tracheostomy or permanent assisted ventilation; defined as > 22 hours daily of mechanical ventilation for more than 1 week (7 days).

will not be excluded from the study.

• History or presence of clinically significant uncontrolled medical conditions (otherthan ALS) that include cardiovascular, respiratory, hepatic, renal,gastrointestinal, endocrinological, hematological, or neurological disorders capableof significantly altering the absorption, metabolism, or elimination of drugs;constituting a risk when taking the study drugs; or interfering with theinterpretation of data as determined by the Investigator.

• Lifetime history of cancer except for basal cell or squamous epithelial carcinomasof the skin that have been resected with no evidence of metastatic disease for 3years. Fully resected basal cell carcinoma and squamous cell carcinoma with noevidence of recurrence for 1 year are permitted.

• Female participants who have a positive serum pregnancy test at Screening, positiveurine pregnancy test on Day 1, or who are breastfeeding on Day 1.

• Has a spinal deformity or other condition that may prevent the performance of alumbar puncture.

• International Normalized Ratio (INR) >1.4, platelet count <50,000/μL, or use ofwarfarin, heparin, or direct oral anticoagulants.

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

• Inability to swallow or tolerate oral medications at Screening.

• Current participation in any other investigational drug study or receipt of aninvestigational drug within 30 days or 5 half-lives (whichever is longer) beforeScreening.

• Known sensitivity to the NB-4746 study drug or any of the formulation components.

• Has received NB-4746 at any time prior to initial Screening.

• Any other reason that, in the opinion of the Investigator, would confound theconduct of this study or the interpretation of the results or that could compromisethe participant's safety.

• Currently taking or planning to receive tofersen for the treatment of ALS.

If a participant does not transition to the OLE in ≤30 days following completion of the main study, the participant will need to be rescreened for laboratory criteria and contraception/pregnancy criteria.