MRG-001 in Patients With Amyotrophic Lateral Sclerosis

Inclusion Criteria:

• Able to provide written informed consent (either from patient or patient's legallyacceptable representative and complying with study procedures, in the PI's opinion.

• Male or female patients between 18-75 years.

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

• Time since onset of weakness due to ALS ≤ 48 months at the time of the ScreeningVisit

• Vital Capacity ≥ 50% of predicted capacity for age, height, and sex at the time ofthe Screening Visit measured by Slow Vital Capacity (SVC), or Forced Vital Capacity (FVC).

• Patients must either not take Riluzole or be on a stable dose of Riluzole for ≥ 30days prior to the Master Protocol Screening Visit. Riluzole-naïve participants arepermitted in the study.

• Participants must either not take Edaravone or have completed at least one cycle ofedaravone prior to the Master Protocol Screening Visit. Edaravone-naïve participantsare permitted in the study.

• Participants must either not take Relyvrio (AMX0035) or be on a stable dose ofRelyvrio for ≥ 30 days prior to the Master Protocol Screening Visit. Relyvrio-naïveparticipants are permitted in the study.

• Women of child-bearing potential (defined as females who are not surgically sterileor who are not over the age of 52 and amenorrhoeic for at least 12 months) mustutilize appropriate birth control throughout the study duration.

• Male patients must agree to use a medically acceptable method of contraception /birth control throughout the study duration.

Exclusion Criteria:

• Subjects who meet one or more of the following criteria will not be consideredeligible to participate in the clinical study:

• Participation in another interventional clinical trial (drug or device) within 30days of Screening and at any time during the study.

• Significant pre-existing organ dysfunction prior to randomization:

• Lung: Receiving supplemental home oxygen therapy at baseline for pre-existingmedical condition (other than COVID-19), as documented in medical record.

• Heart: Pre-existing congestive heart failure defined as an ejection fraction <20% asdocumented in the medical record. Clinically significant ventricular arrhythmias (ventricular tachycardia, ventricular fibrillation), unstable angina, myocardialinfarction (past 3 months), heart and coronary vessel surgery (past 3 months),significant valvular heart disease, uncontrolled arterial hypertension with systolicblood pressure >180 mm Hg and diastolic blood pressure >110 mm Hg.

• Renal: End-stage renal disease requiring renal replacement therapy or creatinineclearance <50 mL/min.

• Hematologic: Baseline platelet count <30,000/mm3 or hemoglobin levels <6.0 g/dL.

• Neurological: Stage ≥3 hepatic encephalopathy by West Haven criteria.

• History of splenectomy or splenomegaly (spleen weighing > 750 g).

• 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.

• 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.

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

• History of splenectomy or splenomegaly (spleen weighing >750 g).

• Co-infection with human immunodeficiency virus (HIV).

• History of organ or bone marrow transplantation, other than a corneal transplant.

or recent (within 3 months) chronic use of immunosuppressive drugs (tacrolimus, mycofenolate mofetil, cyclosporine, rapamycine, hydrochloroquine, azathiopurine, methotrexate), e.g., biologicals, JAK1/2 inhibitors, interferons, interleukins or (prednisone or related corticosteroids are allowed).

• Hypersensitivity to either of the components of MRG-001.

• If female, known pregnancy, or has a positive serum pregnancy test, orlactating/breastfeeding.

• Underlying diseases that, in the opinion of the site investigator, might becomplicated or exacerbated by proposed treatments or might confound assessment ofstudy drug.