A Study of VRG50635 in Participants With Amyotrophic Lateral Sclerosis (ALS)

Inclusion Criteria:

1. Provide written informed consent and be willing and able to comply with therequirements of the study protocol.

2. Must be ≥ 18 and ≤ 75 years of age at the time of signing the informed consent form (ICF).

3. Have a diagnosis of ALS according to the Gold Coast Diagnostic Criteria.

4. Have either sporadic amyotrophic lateral sclerosis (sALS) or familial amyotrophiclateral sclerosis (fALS).

5. Treatment Research Initiative to Cure ALS (TRICALS) risk profile > -6.00 and < -2.00.

6. Have slow vital capacity (SVC) ≥ 60% of the predicted value.

7. Have a score of 3 or 4 on Item #3 (Swallowing) of the Harmonized ALS FunctionalRating Scale-Revised (ALS-FRS-R). Participants with a score of 3 can be enrolledwith the Sponsor's approval only if they are able to safely swallow capsules.

8. Have a body weight ≥ 45 kg and body mass index (BMI) ≥ 18 kg/m2.

9. Participants of childbearing potential are eligible to participate if they are notpregnant or breastfeeding and agree to use one highly effective method ofcontraception, if sexually active, for the duration of the study through 90 daysafter the last study drug administration. Participants must not donate eggs for theduration of study through 90 days after the last dose of study drug.

10. Participants capable of producing sperm and their partners of childbearing potentialmust agree to use condoms and one highly effective method of contraception,respectively, for the duration of the study through 90 days after the last studydrug administration. Participants must not donate sperm for the duration of studythrough 90 days after the last dose of study drug.

11. Be able and willing to undergo measurement of at-home mobility using contactlesssensors connected to the internet.

12. Be able and willing to have clinic or at-home visits during the study.

Exclusion Criteria:

1. Have active psychiatric disease, substance abuse, neuromuscular weakness other thanALS, or any other medical condition that, in the opinion of the Investigator, mightconfound the results of the study or interfere with the intake or absorption of thestudy drug or participation for the full duration of the study.

2. Have a history of unstable or severe cardiac, pulmonary, neurological, oncological,hepatic, or renal disease or another medically significant illness other than ALSprecluding their safe participation in this study.

3. Have a history of substance use disorder or illicit drug use in the last year (medically prescribed or over-the-counter cannabis use is allowed, if legal in thecountry).

4. Have a history of serious infection (e.g., pneumonia, septicemia) ≤ 4 weeks ofScreening; infection requiring hospitalization or treatment with intravenous (IV)antibiotics, antivirals, or antifungals within 4 weeks of Screening; or chronicbacterial infection (e.g., tuberculosis) deemed unacceptable as per theInvestigator's judgment.

5. Had major surgery ≤ 4 weeks before Screening.

6. Be currently taking or planning to take strong cytochrome P450 3A4 (CYP3A4)inhibitors or inducers.

7. Be currently taking or have discontinued treatment with riluzole < 4 weeks beforeScreening. Participants who have been taking a stable dose of riluzole for ≥ 4 weeksare eligible if they remain on the same dose throughout the duration of the study.

8. Be taking Radicava (administered orally or IV as approved in the participant'scountry), Relyvrio, any other approved standard of care treatment, ortauroursodeoxycholic acid (TUDCA) as a dietary supplement administered for < 4 weeksprior to Screening or on a schedule of treatment different from the approvedstandard schedule of treatment. Participants who have completed ≥ 4 weeks oftreatment before Screening are eligible if they plan to continue treatment at astable dose throughout the duration of the study.

9. Have an active malignancy or history (≤ 1 years prior to enrollment) of solid,metastatic, or hematologic malignancy. Exception: basal cell carcinoma in situ ofthe skin that has been adequately treated.

10. Be diagnosed with long QT syndrome. Any history of clinically significantventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation,or Torsades de Pointes) should be discussed with and approved by the study medicalmonitor prior to enrollment.

11. Have a prolonged corrected QT interval using Fridericia's formula (QTcF) at theScreening visit ECG > 450 ms for male participants and > 470 ms for femaleparticipants.

12. Have an active SARS-CoV-2 infection or positive COVID-19 test at Screening.1

13. Have one or more of the following laboratory test abnormalities at Screening: (a)Positive hepatitis C virus (HCV) antibodies with confirmation by HCV-RNA polymerasechain reaction (PCR) reflex testing; (b) Positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb). Note: If a participant is negative forHBsAg but positive for HBcAb, the participant is eligible if the participant testspositive for the antibody to HBsAg reflex testing.

14. Have uncontrolled seizures.

15. Have a documented history of attempted suicide within 6 months prior to theScreening visit, or suicidal ideation of category 4 or 5 on the screeningColumbia-Suicide Severity Rating Scale (C-SSRS), or be at significant risk forsuicide, in the opinion of the Investigator.

16. For participants of childbearing potential, be pregnant or breastfeeding.

17. Have received a live vaccine within 14 days before Screening.

18. Be concurrently participating in any other interventional clinical study or havereceived treatment with another investigational drug within 4 weeks or 5 half-livesof the investigational agent before the Screening visit, whichever is longer.Participation in observational studies is allowed.

19. Have received stem cell or gene therapy for ALS at any time in the past.

20. At the Screening visit, have one or more of the following:

21. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3.0 ×upper limit of normal (ULN)

22. Bilirubin > 1.5 × ULN, unless the participant has documented Gilbert syndrome (isolated bilirubin > 1.5 × ULN is acceptable if bilirubin is fractionated anddirect bilirubin is < 35%)

23. Serum albumin < 3 g/dL

24. Hemoglobin < 9.0 g/dL

25. Platelets < 30,000/μL

26. Estimated glomerular filtration rate < 90 mL/min/1.73 m2 (Modification of Dietin Renal Disease [MDRD])