Phase 2 Placebo-Controlled Study to Assess the Safety and Efficacy of ESK-001 in Active Systemic Lupus Erythematosus

Inclusion Criteria:

Patients with 6 or more months of SLE according to the 2019 EULAR/ACR criteria, have positive autoantibodies or low complement at screening, and have active SLE as measured by SLEDAI-2K of 6 or more, or 4 or more if joint involvement is present.

Patients need to be on treatment which can be:

• A stable dose of oral corticosteroid (≤40 mg/day prednisone or equivalent) for aminimum of 2 weeks prior to signing of the informed consent form (ICF) at theScreening Visit. The dose of oral corticosteroid the patient is taking should notincrease between screening and Week 0 (Day 1).

• And/or antimalarial treatment (e.g., hydroxychloroquine, chloroquine, quinacrine),

• And/or no more than 1 of the following conventional DMARDS:

• Azathioprine ≤200 mg/day

• Mycophenolate mofetil ≤2 g/day or mycophenolic acid ≤1.44 g/day

• Oral, subcutaneous, or intramuscular (IM) methotrexate ≤20 mg/week.

Exclusion Criteria:

• Drug-induced SLE or other autoimmune diseases that, in the opinion of theInvestigator, are likely to confound efficacy assessments

• Active, proliferative lupus nephritis that in the Investigator's opinion may requiretreatment not allowed by the protocol

• Current disease other than SLE that, in the opinion of the Investigator, is likelyto interfere with SLE disease activity assessments. Examples include severefibromyalgia, severe osteoarthritis and severe cardiorespiratory diseases.

• Active severe or unstable neuropsychiatric SLE including, but not limited to thefollowing: aseptic meningitis; cerebral vasculitis; myelopathy; demyelinationsyndromes (ascending or transverse myelitis, acute inflammatory demyelinatingpolyradiculopathy); acute confusional state; impaired level of consciousness;psychosis; acute stroke or stroke syndrome; cranial neuropathy; new seizures;cerebellar ataxia; and mononeuritis multiplex.

• That would make the patient unable to fully understand the ICF, or

• Where, in the opinion of the Principal Investigator, protocol-specified SOC isinsufficient and utilization of a more aggressive therapeutic approach notpermitted in the protocol, is indicated

• Known history of a primary immunodeficiency or an underlying condition such as HIVinfection or splenectomy that predisposes the patient to infection

• Currently active, clinically significant infection of any kind

• Clinically significant chronic infection (eg, osteomyelitis, bronchiectasis) within 8 weeks prior to signing the ICF (chronic fungal nail infections are allowed)

• Any infection requiring hospitalization or treatment with IV anti-infectives notcompleted at least 4 weeks prior to signing the ICF

• Any infection requiring oral anti-infectives (including antivirals) within 2 weeksprior to Day 1

• Any severe herpes infection at any time prior to Week 0 (Day 1), including, but notlimited to, disseminated herpes (ever), herpes encephalitis (ever), recurrent herpeszoster (defined as 2 episodes within 2 years), or ophthalmic herpes (ever)

• Active herpes zoster infection within 12 weeks of prior to signing the ICF

• Active herpes simplex virus within 4 weeks of Day 1

• Other protocol-defined inclusion/exclusion criteria apply