• Medical History/Physical Characteristics; All Cohorts:

• Individuals must not be on a biologic disease-modifying antirheumatic drug (b/tsDMARD) on Day 1 and must have discontinued all b/tsDMARDs (including biosimilars and generics) at least 4 weeks prior to Day 1 with the exception of B cell-depleting agents (eg, rituximab), which must be discontinued for at least 6 months prior to Day 1.

• Ongoing treatment with at least 1 but no more than 2 protocol-permitted conventional synthetic disease-modifying antirheumatic drug (csDMARDs) for at least 12 weeks, at a stable dose for at least 6 weeks prior to Day 1 and remain stable throughout the treatment period:

∙ Use of oral, intramuscular (IM), or subcutaneous(ly) (SC) methotrexate 7.5 to 25 mg/week. Individuals on methotrexate must be receiving folic or folinic acid supplementation at a stable dose.

‣ Oral hydroxychloroquine ≤ 400 mg/day or chloroquine ≤ 250 mg/day.

‣ Oral sulfasalazine 1 to 3 g/day.

‣ Oral leflunomide 10 to 20 mg/day.

• Use of oral corticosteroids of no more than 10 mg prednisone or equivalent per day is allowed if the dose is stable for at least 14 days prior to Day 1. Inhaled corticosteroids for stable medical conditions are allowed but must have been at a stable dose for at least

• 1 week prior to the first dose of study drug. Occasional topical corticosteroids are permitted.

• Where nonsteroidal anti-inflammatory drug (NSAIDs) or acetaminophen are used, the dose must be stable for at least 1 week prior to Day 1

• Individuals must have discontinued all high-potency opiates at least 1 week prior to Day 1.

• Cohort 3 Only:

• Individuals must meet all of the following cohort-specific inclusion criteria, in addition to meeting the inclusion criteria for all individuals , to be eligible for participation in Part B:

• Moderately to severely active RA defined by the following:

• Screening and Day 1:

⁃ 6 or more tender joints on the tender joint count based on 68 joints (TJC68), AND.

⁃ 6 or more swollen joints on the swollen joint count based on 66 joints (SJC66). The distal interphalangeal joints should be evaluated but not included in the total count to determine eligibility.

⁃ Screening Only

⁃ Have a hsCRP ≥ ULN

∙ Inadequate response or intolerance to at least 1 but no more than 3 b/tsDMARDs with no more than 2 mechanisms of action. A lack of response is defined as documented continued or recurrent disease activity after at least 12 weeks of treatment of RA. Intolerance is defined as any documented adverse effect associated with a b/tsDMARD used according to its respective label.

• Laboratory Assessments:

• Cohort 3 Only:

• Anti-cyclic citrullinated peptide antibody (Anti-CCP) positive and/or rheumatoid factor (RF) positive