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

Nonplaque psoriasis or other inflammatory skin conditions

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

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

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 or IL-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 currently enrolled in an investigational study

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

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

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

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

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

History of serious bacterial, fungal, or viral infections that led to hospitalization, or any recent serious infection requiring antibiotic treatment

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

Lab abnormalities indicating significant renal, hepatic or bone marrow dysfunction

History of any immune-mediated or inflammatory medical condition for which participants requires current systemic corticosteroids

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

Known current malignancy or current evaluation for a potential malignancy or history of malignancy within the past 5 years prior to screening, except for adequately treated basal cell or squamous cell skin carcinoma or carcinoma in situ of the cervix

Live vaccines within 4 weeks prior to Study Day 1

Participant has planned surgery during the study period

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

History of mental illness within the last 5 years, unless receiving a fixed regimen of psychiatric medications for at least 6 months before screening or has not required or been prescribed any psychiatric medication within 12 months before screening

Evidence of severe depressive symptoms or active suicidal ideation or behavior