Safety, Tolerability, and Exploratory Efficacy Study of Intrathecally Administered Gene Therapy AMT-162 in Adult Participants With SOD1 Amyotrophic Lateral Sclerosis (SOD1-ALS)

Inclusion Criteria:

• Confirmed clinical and genetic diagnosis of SOD1-mediated ALS (SOD1-ALS)experiencing signs and/or symptoms of lower motor neuron dysfunction (weakness,atrophy, cramps, fasciculations), with or without upper motor neuron symptoms (weakness, bring reflexes, spasticity).

• ALSFRS-R score ≥ 25 at Screening.

• Slow vital capacity (SVC) ≥50% of predicted normal value.

• Capable of providing informed consent and complying with trial procedures,including: medically able to undergo lumbar puncture and has a responsible caregiverable to attend all clinic visit with the Participant.

Exclusion Criteria:

• SOD1 pathogenic or likely pathogenic variants in amino acid regions 43-47.

• Pathogenic repeat expansion in the C9orf72 gene

• Any of the following prior or concomitant treatments:

• Any prior SOD1 suppression therapy with viral microRNA mediators

• Prior SOD suppression therapy with antisense oligonucleotide (ASO) mediatorssuch as tofersen (QALSODY™). Exception: Patients who previously receivedtofersen may be enrolled if the last dose of tofersen was received at least 20weeks prior to the first Screening assessment and if there were no previoustofersen-related SAEs or ongoing tofersen-related adverse events that wouldincrease the risk of receiving AMT-162, per Investigator judgment.

• Other ALS medications riluzole (RILUTEK®, TIGLUTIK®), edaravone (RADICAVA®),and sodium phenylbutyrate and taururosdiol combination (RELYVRIO) orbioequivalents are allowed if dose is stable for 30 days prior toimmunosuppression.

• Any prior administration of an AAV gene therapy.

• Participants must be willing to forego new ALS treatments through at least 6 monthsafter infusion of AMT-162. After 6 months, Investigators and participants may decideto add new ALS medications or change existing ALS medications.