This is a Phase 1, open-label, multi-center safety study of XT-150 in adult participants with Amyotrophic Lateral Sclerosis (ALS).

Participants providing informed consent and meeting all study eligibility criteria will be enrolled in the study and will receive a single injection of XT-150 at the Baseline visit. Follow-up visits will occur over 180 days (6 months) after the injection.

8 participants (4 participants per dose level) will be enrolled sequentially in up to 2 ascending, single dose cohorts: Cohort 1: 1.5 mg XT-150 Cohort 2: 4.5 mg XT-150

The main questions this study is aiming to answer are:

• What adverse events are reported during this study? An adverse event is any "side effect" that participants have during a study. Adverse events may or may not be caused by XT-150. The study doctors will check participants' ALS and general health throughout the trial.
• Does XT-150 have any effects on participants' physical examination findings, vital signs, or laboratory values?

In addition to evaluating the safety of XT-150, this study will also collect samples to provide information on the following:

• The levels of XT-150 in your body
• The effect of XT-150 on cytokines including interleukin (IL)-10
• The effect of XT-150 on relevant ALS biomarkers such as Neurofilament Light (NfL)

In addition, ALS functional score, breathing capacity and strength will be collected over the course of the study.

Key Inclusion Criteria:

• Adults between 18 and 80 years of age
• Male or female, if of childbearing potential or sexually active, strict contraception required
• Have ALS diagnosed by a doctor (specifically, sporadic or familial ALS diagnosed as clinically probable, lab-supported probable or definite ALS defined by the El Escorial criteria)
• Have had symptoms of ALS (muscle weakness) within 36 months of starting this study
• Have the ability to slowly exhale a volume of air at least 60% of what is expected for the participant's sex, height and age
• Have not received treatment for ALS or are currently on a stable dose of an approved treatment for ALS. Patients currently receiving Tofersen are not eligible.
• Able to receive the study injection intrathecally, determined by the study doctor
• Able to undergo the study procedures and adhere to the study visit schedule at the time of study entry, with an estimated life expectancy of 6 months or greater

Key Exclusion Criteria:

• Have an implanted shunt to drain cerebrospinal fluid (CSF) or an implanted CNS catheter
• Have an implanted of diaphragm pacing system
• Tracheostomy
• History or current diagnosis of cardiac conditions or ECG abnormalities indicating significant risk of safety for participants in the study
• History or current diagnosis of respiratory conditions such as COPD
• History or current diagnosis of cancer, chemical meningitis, HIV, Hep B, Hep C, uncontrolled diabetes
• Presence of an autoimmune condition (for example, rheumatoid arthritis or lupus) requiring treatment or immunodeficiency
• Clinical or laboratory evidence of hepatic or renal disease/injury.
• Taking any prohibited medications
• Women who are pregnant or nursing
• Use of any investigational drugs or devices within 30 days or 5 half-lives of the study agent (whichever is longer). Exception: Observational, non-interventional clinical studies are allowed in the opinion of the study doctor.
• Any other condition that the study doctor feels could compromise the participant's safety, ability to communicate with the study staff, or the quality of the data