Study of S-4321 in Participants With an Autoimmune or Immune-mediated Disease

Exclusion Criteria

• •1. Have received a PD-1 agonist, immune checkpoint agonist, immune checkpoint inhibitor, anti-CD19 or anti-CD20 agents, cell therapy, B cell modulating agents, alkylating agents, or any other immune cell depleting therapy.
• •2. Have received azathioprine, cyclosporine, mycophenolate mofetil, or tacrolimus within 4 weeks
• •3. Unable or unwilling to discontinue a prohibited medication
• •4. Presence of clinically relevant immunosuppression
• •5. Current infection or history of severe infection
• •6. Any history of malignant disease, with some exceptions
• •Major inclusion/exclusion for each autoimmune or immune-mediated disease:
• •For RA:
• •1. Confirmed diagnosis of moderate to severe active RA by the American College of Rheumatology (ACR) 2010/European League Against Rheumatism (EULAR) criteria for at least 3 months prior to the Screening 1 visit, and:
• •1. ≥6 swollen joint count based on 66 joint count
• •2. ≥6 tender joint count based on 68 joint count
• •3. Seropositive for RF and/or ACPA
• •4. Elevated hsCRP ≥1.2 times greater than the ULN
• •5. Does not have Class IV RA according to ACR revised criteria
• •2. Inadequate response to, or loss of response, or intolerance to:
• •1. \>1 conventional synthetic DMARD after 3 months of therapy OR
• •2. \>1 biologic DMARD/targeted synthetic DMARD after 3 months of therapy
• •3. Has not failed 3 or more bDMARDs and/or tsDMARDs
• •For PsA:
• •1. Confirmed diagnosis of adult-onset PsA classified by the Classification Criteria for Psoriatic Arthritis (CASPAR) for at least 3 months prior to the Screening 1 visit, with all of the following:
• •1. Active PsO defined by at least 1 psoriasis lesion
• •2. Active disease defined by \>3 swollen joints and \>3 tender joints using the 76/78 swollen and tender joint count
• •2. Received standard doses of NSAIDs for \>4 weeks or csDMARDs for \>3 months and has been on a stable dose for \>8 weeks, or participant has intolerance to NSAIDs or DMARDs
• •3. Participants may be TNF inhibitor therapy naïve or may have received 1 prior TNF inhibitor
• •4. Has not had inadequate response or intolerance to 2 or more bDMARDs or csDMARDs
• •For PsO:
• •1. Confirmed diagnosis of moderate to severe plaque PsO for at least 6 months, with all of the following:
• •1. Psoriasis Area and Severity Index (PASI) \>12 points
• •2. Static Physician's Global Assessment (sPGA) \>3 points
• •3. Body surface area (BSA) of PsO involvement \>10%
• •2. Cannot have a clinically significant flare within 12 weeks
• •3. Does not have history of erythrodermic psoriasis, generalized or localized pustular psoriasis, predominantly guttate psoriasis, or medication-induced or medication-exacerbated psoriasis
• •4. Has not had inadequate response to more than 2 prior bDMARDs
• •For CLE (with or without systemic manifestations):
• •1. Histologically confirmed diagnosis of CLE with or without systemic manifestations for at least 6 months
• •2. Has active skin manifestations as measured by CLASI-A \>10 or CLASI-A \>8, if there is no alopecia or mucous membrane lesions
• •3. Participant must have an active CLE lesion despite an adequate trial of antimalarial treatment for at least 6 months.
• •4. Cannot have active lupus nephritis or moderate-to-severe or chronic kidney disease with eGFR \<45 mL/min/1.73m2
• •5. Cannot have active neuropsychiatric SLE
• •For AD:
• •1. Confirmed diagnosis of AD as defined by the American Academy of Dermatology: Guidelines of Care for the Management of Atopic Dermatitis for at least 12 months
• •1. Eczema Area and Severity Index (EASI) \>16
• •2. Validated Investigator Global Assessment (vIGA-AD) \>3
• •3. BSA of AD involvement \>10%
• •4. PP-NRS) \>4 (average of daily scores) during the 7 days prior to dosing
• •2. Inadequate response to existing topical medications within 6 months or has a history of intolerance to topical therapy as defined by at least 1 of the following:
• •1. Inability to achieve good disease control after use TCS for at least 4 weeks
• •2. Documented history of clinically significant AEs with the use of TCS
• •3. Failed systemic therapies intended to treat AD within 6 months