A Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Of AJ201 In Patients

Inclusion Criteria:

1. Able to give informed consent before any assessment is performed.

2. Adult males aged 18 or greater with a confirmed genetic diagnosis (confirmed CAGrepeat expansion in the AR gene of at least 36 repeat) of SBMA and clinicaldiagnosis of symptomatic muscle weakness.

3. Able to complete 2MWT with or without the aid of an assisted device at screening.

4. SBMAFRS score ≥26 (subjects with moderate to high physical performance) atscreening.

5. Willing to participate in all aspects of study design and assessments, includingblood draw and muscle biopsies.

6. Male subjects and their female spouses/partners who are of childbearing potentialmust agree to use highly effective contraception consisting of 2 forms of birthcontrol (at least 1 of which must be a barrier method) starting from the first doseof the study drug and continuing throughout the study period and for 90 days afterthe last dose of the study drug. Male subjects should also not donate sperm duringthe study and for 90 days after the final administration of the study drug.

7. Able to communicate well with the Investigator, to understand, and comply with therequirements of the study.

Exclusion Criteria:

1. Nonambulatory.

2. Contraindications to MRI such as a contraindicated nonremovable metal device (ie,pacemaker, defibrillator, insulin pump, metal clips, nonremovable jewelry) orclaustrophobia.

3. Use of other investigational products within 30 days, or within 5 half-lives,whichever is longer, prior to the first dosing, or until the expected PD effect hasreturned to baseline, whichever is longer. Approved COVID-19 vaccines are notconsidered investigational treatments and are allowed prior to, during, and afterthe study.

4. Use of drugs known to affect muscle metabolism within the previous 1 month prior tothe first dosing, including (but not limited to) systemic corticosteroids (>10mg/day prednisone or equivalent), androgens, or androgen reducing agents, systemicbeta agonists or beta blockers, and relevant herbal, or nutraceutical products. Forsubjects using systemic corticosteroids (≤10 mg/day or equivalent), they should beon stable dose for the previous 3 months prior to first dosing.

5. Known history of allergic reactions to curcumin analogs or excipients in the studydrug formulation.

6. Known history of clinically significant cardiovascular disease (includinguncontrolled hypertension, ischemic heart disease [eg, myocardial infarction,angina, abnormal coronary arteriography or cardiac stress testing/imaging]), heartfailure or left ventricle dysfunction of New York Heart Association ClassificationIII-IV, or clinically significant cerebrovascular disease (stroke or transientischemic attacks).

7. An abnormal ECG at screening visit which is judged to be clinically relevant andrepresents an unacceptable risk for study participation by the Investigator. Anexample is Brugada-like ECG changes which have been reported in SBMA patients inItaly and Japan.

8. Any surgical or medical condition which may jeopardize the subject in case ofparticipation in the study. The Investigator should make this determination inconsideration of the subject's medical history and/or clinical or laboratoryevidence of any of the following during screening:

9. Liver disease or liver injury as indicated by abnormal liver function testssuch as AST, ALT, gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP),or serum bilirubin in the presence of normal serum creatine kinase (CK).

10. Significant swallowing dysfunction, which may increase the risk of accidentalchoking and aspiration pneumonia.

11. Subjects with renal impairment defined as a creatinine clearance of <90 mL/min atscreening. (Creatinine Clearance = [140 - age in years] weight in kg]/[72serumCr(mg/dL)]).

12. History of active tuberculosis or exposure to endemic areas within 8 weeks prior toQuantiFERON®-TB testing performed at screening.

13. Positive QuantiFERON®-TB indicating possible tuberculosis infection.

14. History of immunodeficiency diseases, including a positive HIV test result atscreening.

15. A positive hepatitis B surface antigen or hepatitis C test result at screening.

16. Subjects with known bleeding disorders, or who are under treatment withanticoagulants or with a platelet count <50,000 (due to the increased risk ofbleeding during muscle biopsy procedure).

17. History of drug or alcohol abuse within the 12 months prior to the first dosing, orevidence of such abuse as indicated by the laboratory assays conducted duringscreening.

18. The Investigator should be guided by the following criteria during screening: a. Anysingle laboratory parameter may not exceed 3 times the upper limit of normal (ULN).A single parameter elevated up to and including 3 times the ULN should be re-checkedonce more as soon as possible, and in all cases, at least prior toenrollment/randomization, to rule out lab error. For abnormal liver function tests,in the presence of elevated serum CK levels, ALT, or AST, up to 5 times the ULN areacceptable if other liver tests are normal. b. If the total bilirubin concentrationis increased above 1.5 times the ULN, total bilirubin should be differentiated intothe direct and indirect reacting bilirubin. In any case, serum indirect bilirubinshould not exceed the value of 1.6 mg/dL (27 mol/L).

19. Use of drugs that are inhibitors of CYP3A4, 2B6, or 2C19 within 2 weeks prior to thefirst dosing and during the study.

20. Use of drugs that are substrates of MATE1 or MATE2-K transporters within 2 weeksprior to the first dosing and during the study.

21. Use of turmeric or products containing curcumin within 2 weeks prior to the firstdosing and during the study.

22. Use of aspirin or nonsteroidal anti-inflammatory agents within 3 days prior to thebaseline visit (due to the increased risk of bleeding during muscle biopsyprocedure).

23. Any reason that, in the opinion of the Investigator, would prevent the subject fromparticipating in the study.