Rho Kinase (ROCK) Inhibitor in Tauopathies - 1

1. Between 35 and 80 years of age (inclusive).

2. Able to walk at least 10 steps with minimal assistance (stabilization of one arm or use of cane/walker).

3. MRI at Screening is consistent with the underlying neurodegenerative disease of the respective diagnostic cohort (i.e. PSP-RS or CBS), with no large strokes or severe white matter disease.

4. Mini-Mental State Exam (MMSE) at Screening is between 20 and 30 (inclusive).

5. For CBS: Amyloid beta (Aβ) positron emission tomography (PET) scan (florbetapir or equivalent) at Screening is not consistent with underlying Alzheimer's disease (AD). Previous Aβ PET scan negativity (assessed by a certified neuroradiologist) or previous AD CSF biomarker (Aβ/tau level, P-tau181 or Aβ1-40 / Aβ1-42) or plasma AD biomarker (P-tau181 or P-tau217) negativity may be used instead of performing an Aβ PET scan at Screening at the Principal Investigator's (PI's) discretion.

6. The following medications are allowed, but must be stable for 2 months prior to Baseline:

1. FDA-approved AD medications

2. FDA-approved Parkinson's Disease (PD) medications

7. Other prescription medications are allowed as long as the dose is stable for 30 days prior to Baseline. (Note Exclusion Criteria 17 and 18.)

8. Has a reliable study partner who agrees to accompany the participant to visits, and spends at least 5 hours per week with the participant.

9. Signed and dated written informed consent obtained from the participant/legally authorized representative (LAR) and the participant's study partner in accordance with local Institutional Review Board (IRB) regulations.

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

11. Males must agree to abstain from sex with WCBP or use an adequate method of contraception for the duration of the study drug treatment period and for 75 days after.

For PSP-RS Only

12. Meets 2017 consensus criteria for possible or probable progressive supranuclear palsy-Richardson syndrome (PSP-RS).

For CBS Only

13. Meets 2013 consensus criteria for possible or probable corticobasal degeneration (CBD), CBS subtype

1. Meets criteria for probable AD established by the National Institute on Aging and the Alzheimer's Association (NIA-AA).

2. Any other medical condition other than PSP-RS or CBS that could account for cognitive or motor deficits (e.g., active seizure disorder, stroke, vascular dementia, substance abuse or alcoholism).

3. History of a prominent and sustained response to levodopa therapy in the opinion of the PI.

4. Presence of significant cardiovascular, hematologic, renal, or hepatic disease.

5. Suicidal ideation per the Columbia-Suicide Severity Rating Scale (C-SSRS) that in the opinion of the PI would pose a safety risk or interfere with the appropriate interpretation of study data

6. History of major psychiatric illness or untreated depression that in the opinion of the PI would pose a safety risk or interfere with the appropriate interpretation of study data.

7. Neutrophil count <1,500/mm3, platelets <100,000/mm3, total bilirubin ≥1.5 x Upper Limit of Normal (ULN), alanine aminotransferase (ALT) ≥3 x ULN, aspartate aminotransferase (AST) ≥3 x ULN, or International Normalized Ratio (INR) >1.2.

8. Serum creatinine >1.3 mg/dL.

9. Evidence of any clinically significant findings on screening or baseline evaluations which, in the opinion of the PI would pose a safety risk or interfere with appropriate interpretation of study data.

10. Current or recent history (within four weeks prior to Screening) of a clinically significant bacterial, fungal, or mycobacterial infection.

11. Current clinically significant viral infection.

12. Major surgery within four weeks prior to Screening.

13. Any contraindication for MRI or unable to tolerate MRI scan at Screening.

14. Any contraindication to or unable to tolerate lumbar puncture at Screening, including use of anticoagulant medications such as warfarin. Daily administration of aspirin up to 81mg is not a contraindication, as long as the dose is stable for 30 days prior to Screening.

15. Participants who, in the opinion of the PI, are unable or unlikely to comply with the dosing schedule or study evaluations.

16. Treatment with another investigational drug within 30 days or 5 half-lives of drug before Baseline, whichever is longer. Treatment with investigational drugs other than fasudil while on study will not be allowed.

17. Treatment with systemic corticosteroids within 30 days or 5 half-lives of drug before Baseline, whichever is longer.

18. On more than one of the following drug classes: long-acting nitrates, beta-blockers, or calcium channel blockers.

19. Known hypersensitivity to the inactive ingredients in the study drug (fasudil).

20. Known to be pregnant or lactating; or positive pregnancy test at Screening or Baseline (Day 1) for WCBP.

21. Cancer within 5 years of Screening, except for basal cell carcinoma.

22. History of serum or plasma progranulin level less than one standard deviation below the normal participant mean for the laboratory performing the assay.

23. History or evidence at Screening of known disease-associated mutations in GRN, TBK1, C9ORF72, TARBP, CHMPB2, or VCP genes (FTLD causative gene mutations not associated with underlying tau pathology).

24. Blood pressure < 90/60.

25. Evidence of orthostatic hypotension.