Rho Kinase Inhibitor in Amyotrophic Lateral Sclerosis (REAL)

Inclusion Criteria:

1. Between 18 and 75 years of age (inclusive) at Screening 1.

2. Subject has had a diagnosis of probable laboratory-supported, probable, or definiteALS (as defined by El Escorial Revised ALS diagnostic criteria) by Screening 1, andno other cause of the neurological impairment has been identified.

3. Average decrease in ALSFRS-R of 0.5 to 3 (inclusive) points per month, calculatedusing: Cohort 1 - the most recent historical ALSFRS-R score from at least 3 monthsprior to Screening 1. If there is no qualifying previous score, an estimated ratewill be calculated using the historical date of ALS symptom onset (weakness and/ordysarthria and/or dysphagia). Cohort 2 - the historical date of ALS symptoms onset.

4. Percent predicted SVC ≥ 50% at Screening 1.

5. ALS symptom onset (weakness and/or dysarthria, and/or dysphagia) within 48 months ofScreening 1.

6. Subjects taking riluzole, edaravone, or phenylbutyrate (PB) and/ortauroursodeoxycholic acid (TUDCA) may be included if the following criteria are metat Screening 1, and there is no change in treatment between Screening 1 andEnrollment:

• Stable dose of riluzole for at least 30 days;

• Stable dose of edaravone for at least 3 cycles; and/or

• Stable dose of PB and/or TUDCA for at least 90 days Subjects taking any of these drugs prior to screening who intend to discontinue thembefore starting the study must have discontinued the drug(s) at least 28 days beforeScreening 1.

7. Women of childbearing potential (WCBP) must agree to abstain from sex or use anadequate method of contraception for the duration of the screening period, the studydrug treatment period, and for 28 days after the last dose of study drug.

8. Males must agree to abstain from sex with WCBP or use an adequate method ofcontraception for the duration of the study drug treatment period and for 75 daysafter.

9. Capable of providing informed consent and following trial procedures (where subjectconsents but is unable to sign the informed consent a legally authorizedrepresentative (LAR)/surrogate must sign on their behalf).

Exclusion Criteria:

1. ALSFRS-R < 24 at Screening 1.

2. Expected change in dosing of riluzole, edaravone, or PB and/or TUDCA betweenScreening 1 and the end of the study.

3. Presence of other causes of neuromuscular weakness or other neurodegenerativediseases that could interfere with the objectives of the study or the safety of thesubject, in the opinion of the Investigator.

4. Mechanical ventilation via tracheostomy. (Use of non-invasive ventilation e.g.,continuous positive airway pressure, non-invasive bi-level positive airway pressureor non-invasive volume ventilation is not an exclusion).

5. Any medical condition (including cardiovascular, hematologic, renal, hepatic, orpsychiatric diseases) that in the opinion of the Investigator would disallow safeparticipation in the trial or interpretation of the study results.

6. Suicidal ideation per the Columbia-Suicide Severity Rating Scale (C-SSRS) that inthe opinion of the Investigator would pose a safety risk.

7. ALT ≥ 3 x upper limit of normal (ULN) or aspartate aminotransferase (AST) ≥ 3 x ULNat Screening.

8. Estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73m2 at Screening.

9. Participants who, in the opinion of the Investigator, are unable or unlikely tocomply with the dosing schedule or study evaluations.

10. Treatment in a clinical trial with another investigational drug within 28 days or 5half-lives of drug before Screening 1, whichever is longer.

11. Exposure at any time to any gene therapies under investigation for the treatment ofALS.

12. Treatment with clenbuterol within 28 days of Screening 1, or any time betweenScreening 1 and enrollment.

13. On more than one of the following drug classes: long-acting nitrates, beta-blockers,or calcium channel blockers. (Note: subjects may be on one of the drug classes.)

14. Systolic blood pressure < 90 mmHg and/or diastolic blood pressure < 60 mmHg atScreening. (Note: in the case of a systolic blood pressure < 90 and/or diastolicblood pressure < 60, BP measurements should be repeated after 10 minutes, and thehigher reading used for Inclusion/Exclusion.)

15. Known hypersensitivity to the active (fasudil) or inactive ingredients in the studydrug.

16. Known to be pregnant or lactating; or positive pregnancy test for WCBP.

17. For Cohort 1 only: At Screening 2, neutrophil count < 1,500/mm3, platelets < 100,000/mm3, international normalized ratio (INR) > 1.5 or any contraindication toor unable to tolerate lumbar puncture, including use of anticoagulant medicationsthat cannot be withheld. For example, if a subject is taking warfarin and it cannotbe withheld for lumbar puncture, this would exclude the subject from study entry.