A Study to Evaluate the Efficacy and Safety of ESK-001 in Patients With Moderate to Severe Plaque Psoriasis

Inclusion Criteria:

1. Males or females, age ≥18 years

2. Diagnosis of plaque psoriasis for ≥6 months

3. Plaques covering ≥10% of BSA

4. PASI ≥12

5. sPGA ≥3

6. Women of childbearing potential (WOCBP) and males who are sexually active with WOCBPmust agree to adhere to highly effective methods of contraception

Exclusion Criteria:

1. Nonplaque psoriasis or other inflammatory skin conditions

2. immune-mediated conditions commonly associated with psoriasis (eg inflammatory boweldisease). Participants with psoriatic arthritis may participate

3. Pregnant, lactating, or planning to get pregnant during the study

4. Use of drugs prior to Study Day 1 that treat or may affect psoriasis:

• Topical within 2 weeks

• Phototherapy or any systemic treatments within 4 weeks

• Any biologic agent targeted to IL-12 or IL-23 within 6 months, oral IL-12 orIL-23 or TNFα inhibitor within 2 months, or IL-17 within 4 months

• Systemic immunosuppressants or immunomodulatory drugs within 4 weeks

• Modulators of B cells within 6 months, or T cells within 3 months

• JAK inhibitors or TYK2 inhibitors within 4 weeks

• PDE4 inhibitor within 2 months

• Any investigational agent, within 30 days or 5 half-lives or is currentlyenrolled in an investigational study

5. Lack of clinical response to a TYK2, IL-12, or IL-23 targeted psoriasis treatment

6. Participants with QTcF >450 msec (males) or >470 msec (females) at Screening

7. Unstable cardiovascular disease, defined as a recent clinical deterioration or acardiac hospitalization within the last 3 months

8. Evidence of recent or recurrent herpes zoster or herpes simplex viral infection

9. Evidence of active infection or positive test result for hepatitis B, hepatitis C,HIV or TB

10. History of serious bacterial, fungal, or viral infections that led tohospitalization, or any recent serious infection requiring antibiotic treatment

11. Any history of known or suspected congenital or acquired immunodeficiency state orcondition that would compromise the participant's immune status

12. Lab abnormalities indicating significant renal, hepatic or bone marrow dysfunction

13. History of any immune-mediated or inflammatory medical condition for whichparticipants requires current systemic corticosteroids

• Stable doses of inhaled corticosteroids for treatment of asthma are allowed

14. Known current malignancy or current evaluation for a potential malignancy or historyof malignancy within the past 5 years prior to screening, except for adequatelytreated basal cell or squamous cell skin carcinoma or carcinoma in situ of thecervix

15. Live vaccines within 4 weeks prior to Study Day 1

16. Participant has planned surgery during the study period

17. Any acute or chronic illness/condition or evidence of an unstable clinical conditionthat, in the opinion of the Investigator, will substantially increase the risk tothe participant if he or she participates in the study

18. History of mental illness within the last 5 years, unless receiving a fixed regimenof psychiatric medications for at least 6 months before screening or has notrequired or been prescribed any psychiatric medication within 12 months beforescreening

19. Evidence of severe depressive symptoms or active suicidal ideation or behavior