Proof of Concept Study of AX-158 in Patients With Mild to Moderate Plaque Psoriasis

Inclusion Criteria:

1. Able to understand and willing to provide informed consent and able to comply withthe study procedures and restrictions.

2. Diagnosis of plaque psoriasis for ≥3 months at time of screening.

3. Male or female subjects age 18 to 60 years, inclusive, at the time of informedconsent.

4. Body mass index (BMI) 18 to 40 kg/m2, inclusive, where BMI (kg/m2) is calculated bybody weight (kg)/height2 (m2).

5. Female subjects may be enroled if the following criteria are met:

6. Documented to be surgically sterile or postmenopausal or practicing trueabstinence for at least 28 days prior to investigational product (IP)administration until 30 days (duration of ovulatory cycle) after the last IPadministration and having a negative serum pregnancy test at screening and anegative urine pregnancy test within 24 hours prior to the start of IPadministration, or

7. Women of childbearing potential (WOCBP) must have a negative serum pregnancytest at screening and a negative urine pregnancy test within 24 hours prior tothe start of IP administration.

8. WOCBP must agree to follow instructions for methods of contraception asdescribed in Appendix 18.2 for the duration of treatment with IP plus 5half-lives of IP (50 hours) plus 30 days (duration of ovulatory cycle) afterthe last IP administration.

9. Women must not be pregnant, lactating, breastfeeding, or planning pregnancyduring the study period.

10. Male subjects who are sexually active with WOCBP may be enrolled if they are

11. Documented to be surgically sterile (vasectomy), or

12. Practicing true abstinence for 90 days after the last IP administration, or

13. Males who are sexually active with WOCBP must agree to follow instructions formethods of contraception for the duration of treatment with IP plus 5half-lives of the IP plus 90 days (duration of sperm turnover) after the lastIP administration. In addition, male subjects must be willing to refrain fromsperm donation during this time.

14. Azoospermic males are exempt from contraceptive requirements. WOCBP who arecontinuously not heterosexually active are also exempt from contraceptiverequirements and must still undergo pregnancy testing as described in inclusioncriterion #6b.

15. Fully vaccinated for COVID-19 per local regulations and site standard of care (SOC).

Exclusion Criteria:

1. Diagnosis of non-plaque psoriasis (guttate, inverse, pustular, erythrodermic).

2. Diagnosis of psoriatic arthritis, uveitis, inflammatory bowel disease, or otherimmune-mediated conditions that are commonly associated with psoriasis for which asubject requires current systemic (oral, subcutaneous, or intravenous [IV]) (including corticosteroids, immunosuppressants, biologics) immunosuppressant medicaltreatment. Certain therapies such as non-steroidal anti-inflammatory drugs may bepermitted at the discretion of the medical monitor.

3. Psoriasis affecting the scalp only.

4. Inability to tolerate oral medication.

5. A clinically significant history of gastrointestinal disorder likely to influenceabsorption of IP.

6. Evidence of renal, hepatic, central nervous system, respiratory, cardiovascular, ormetabolic dysfunction.

7. Participation in a clinical study and/or receipt of an IP within the previous 3months or 5 half-lives, whichever is longer, before administration of the first doseof IP.

8. History or evidence of active infection and/or febrile illness within 7 days offirst administration of IP.

9. History of serious bacterial, fungal, or viral infections that requiredhospitalization and IV antibiotic treatment within 90 days prior to screening, orany recent serious infection requiring antibiotic treatment within 30 days of IPadministration.

10. Has received a live vaccine within 60 days of first dose of IP.

11. Current clinical radiographic or laboratory evidence of active tuberculosis (TB), orany history of or significant risk for TB.

12. Any major surgery within 4 weeks of IP administration.

13. Has unstable cardiovascular disease, defined as a recent clinical deterioration (eg,unstable angina, rapid atrial fibrillation) in the last 3 months or a cardiachospitalization within the last 3 months.

14. History of malignancy (solid organ or hematologic including myelodysplasticsyndrome) or lymphoproliferative disease within the previous 5 years (other thanresected cutaneous basal cell or squamous cell carcinoma that has been treated withno evidence of recurrence).

15. Has used topical medications/treatments that could affect psoriasis or sPGAevaluation (including, but not limited to, mild to moderate corticosteroids [eg,hydrocortisone cream, triamcinolone acetonide], calcineurin inhibitor, calcipotriol,salicylic acid/other keratolytic, coal tar, short contact dithranol) within 4 weeksof the first administration of IP.

16. Has received phototherapy that could affect psoriasis or sPGA evaluation (eg,narrowband ultraviolet B [UVB] psoralen [oral or topical] with local UVA) within 4weeks of the first administration of IP.

17. Has received any systemic non-biologic medications/treatments (including, but notlimited to, methotrexate, ciclosporin, acitretin, and apremilast) or any systemicbiologic medications/treatments (including, but not limited to etanercept,efalizumab, infliximab, adalimumab, ustekinumab, secukinumab, and ixekizumab) thatcould affect psoriasis or sPGA evaluation within 4 weeks of the first administrationof the IP.

18. Chest X-ray findings suspicious of infection at screening. Subjects may berescreened and if deemed eligible may be randomized within 28 days of completing anappropriate course of antibiotic treatment for pulmonary infection. If a chest X-rayhas been performed within 6 months of the screening visit and the report and resultsare available, then a chest X-ray is not required at the screening visit.

19. Clinically significant history of previous allergy and/or sensitivity to AX-158 orany of the excipients contained within AX-158.

20. Clinically significant abnormal test results for serum biochemistry, hematology,and/or urine analyses within 28 days prior to first dose administration of the IP:

21. Leukopenia defined as absolute white blood cell count <3000/mm3 within 28 daysof dosing with IP on Day 1.

22. Lymphopenia defined as absolute lymphocyte count <500/mm3 within 28 days ofdosing with IP on Day 1.

23. Neutropenia defined as absolute neutrophil count <1000/mm3 within 28 days ofdosing with IP on Day 1.

24. Moderate to severe thrombocytopenia defined as platelet count <100,000/mm3within 28 days of dosing with IP on Day 1.

25. Moderate to severe anemia defined as hemoglobin <9 g/dL within 28 days ofdosing with IP on Day 1.

26. Total serum bilirubin, alkaline phosphatase, aspartate transaminase and alaninetransaminase >1.5 × upper limit of normal (ULN). If total bilirubin is abovethe ULN and is then fractionated, direct bilirubin must be within normallimits.

27. Subject with a positive urinary drug screen (including alcohol and cotinine) testresults, determined within 28 days before the first dose administration of the IP. Apositive test result may be repeated at the investigator's discretion.

28. Clinically significant abnormalities in 12-lead electrocardiogram (ECG) determinedwithin 28 days before first dose of IP including a QRS >120 ms, PR interval >220 msand QT interval corrected using Fredericia's formula >450 ms.

29. Clinically significant abnormalities in vital signs and physical examinationdetermined within 28 days before first dose of IP.

30. Subjects with a positive COVID-19 test on admission per local regulations and siteSOC.

31. Any other condition that, in the investigator's judgement, will substantiallyincrease the risk to the subject if they participate in the study.