Systemic Lupus Erythematosus (SLE) Clinical Trials

⁃ Participant must be 18 (or the legal age of consent in the jurisdiction in which the study is taking place) to 65 years of age, inclusive, at the time of signing the informed consent.

⁃ For RA participants, only:

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⁃ Diagnosis of RA as defined by the 2010 EULAR/ACR classification criteria

⁃ Positive for ≥ 1 disease-specific autoantibody performed by the central laboratory.

⁃ (a) RF (b) ACPA

⁃ Moderate or severe disease activity defined as:

• DAS28-CRP \> 3.2 AND

• 4 tender joints and ≥ 4 swollen joints

• (a) US-Specific Criterion: DAS28-CRP \> 3.2 AND ≥ 6 tender joints and ≥ 6 swollen joints 4. Intolerance to or inadequate response following approximately 3 month's treatment or longer to ≥2 b/tsDMARDs (with different mechanisms of action) after failing csDMARD therapy (unless csDMARD therapy is contraindicated). There is no minimum duration for taking a treatment in cases of intolerance.

• 5\. Background standard of care is not a requirement for participation, however, the following therapies are permitted and may be continued during the study (alone or in combination). Any other systemic immunosuppressive treatment or immune modulating biologic drug must be discontinued in line with the washout periods listed in Inclusion Criterion 12:

• (a) Oral prednisone (or equivalent). Dose must be stable and ≤ 10mg a day for ≥ 2 weeks prior to Day 1. (b) Oral anti-malarial (e.g. hydroxychloroquine ≤ 400 mg a day). Dose must be stable for ≥ 4 weeks prior to Day 1. (c) Treatment with one of the following csDMARDs for ≥ 3 months and at a stable dose for ≥ 4 weeks prior to Day 1. (i) Methotrexate ≤ 25 mg per week, without change of route of administration for 8 weeks prior to Day 1 (ii) Sulfasalazine ≤ 3g/day (iii) Leflunomide ≤ 20 mg/day 3. For SLE participants, only:

‣ Diagnosis of SLE as defined by the 2019 EULAR/ACR classification criteria

‣ Positive for ≥ 1 disease-specific autoantibody performed by the central laboratory. If autoantibodies are negative on central laboratory test, documented history of test results may be used. (a) ANA immunofluorescent assay test (titer ≥ 1:80) (a) Anti-dsDNA (b) Anti-Sm.

‣ Moderate or severe disease activity defined as clinical SLEDAI-2K \> 4

∙ (a) US-specific criterion: clinical SLEDAI-2K ≥ 6

‣ Intolerance to or inadequate response following approximately 3 months treatment or longer ≥ 3 SoC (includes: corticosteroids, anti-malarial drugs, calcineurin inhibitor, methotrexate, azathioprine, leflunomide, mycophenolic acid or its derivatives, cyclophosphamide, belimumab, anifrolumab, telitacicept, or B-cell depleting monoclonal antibodies). There is no minimum duration for taking a treatment in cases of intolerance.

‣ Background standard of care is not a requirement for participation, however, the following therapies are permitted and may be continued during the study (alone or in combination). Any other systemic immunosuppressive treatment or immune modulating biologic drug must be discontinued in line with the washout periods listed in Inclusion Criterion 12: (a) Oral prednisone (or equivalent. Dose must be stable and ≤ 20mg a day for ≥ 2 weeks prior to Day 1. (b) Oral anti-malarial (eg, hydroxychloroquine ≤ 400 mg a day). Dose must be stable for ≥ 4 weeks prior to Day 1. (c) Treatment with one of the following immunosuppressive treatments. for ≥ 3 months and at a stable dose for ≥ 4 weeks prior to Day 1. (i) Methotrexate ≤ 25 mg/week, without change of route of administration for 8 weeks prior to Day 1 (ii) Mycophenolate mofetil or equivalent ≤ 2 g/day (dose must be ≤ 2 g/day for 3 months prior to Day 1) (iii) Azathioprine ≤ 200 mg/day (iv) Leflunomide ≤ 20 mg/day (v) Tacrolimus ≤ 0.1 mg/kg/day with maximum dose of 5 mg/day (vi) Cyclosporin ≤ 3 mg/kg/day with maximum dose of 200 mg/day

• 4\. Blood B cells ≥ 50 cells/μL at screening. 5. IgG levels ≥ 6 g/L at screening. 6. Eligibility for re-treatment of previously treated participants only. The following criterion applies only to participants being considered for re-treatment and is not applicable to participants undergoing initial screening for study entry.

• 1\. Participants treated in prior study cohorts who did not experience an IMP-related DLT or discontinue treatment and/or participation due to an IMP-related AE are eligible for re-treatment in Parts 2 and 3. Participants must otherwise meet all protocol-defined eligibility criteria, with the exception of Inclusion Criterion 17 (B cell count), and meet one of the 2 criteria below:

‣ Completed the 6-month treatment period OR

‣ Completed a minimum of 90 days in the treatment period and have peripheral B cell counts that are ≥ 90% of baseline or above lower limit of normal (LLN)