A Phase 2 Master Protocol Assessing Inebilizumab and Blinatumomab in Autoimmune Diseases

Inclusion Criteria:

• Subprotocol A and B: Diagnosis of SLE according to 2019 European League AgainstRheumatism and the American College of Rheumatology (ACR) classification criteria.

• Subprotocol A and B: Participant must be positive for at least one of the followingautoantibodies at screening (performed by central laboratory) or through documentedhistory:

1. Antinuclear antibodies (ANA) ≥ 1:80

2. Anti-double stranded deoxyribonucleic acid (anti-dsDNA) antibodies elevated toabove normal range (ie, positive results)

3. AntiSmith antibodies elevated to above normal (ie, positive results).

• Subprotocol A and B (Subgroup 1): Active, biopsy-proven, proliferative LNdemonstrating class III or class IV with or without co-existing features of Class VLN (or pure Class V LN for Subprotocol B only) according to 2018 InternationalSociety of Nephrology/Renal Pathology Society (ISN/RPS) criteria. The local biopsyreport will be used.

• Subprotocol A and B: SLE Disease Activity Index 2K ≥ 6.

• Subprotocol A and B (Subgroup 1): Inadequate response, loss of response orintolerance to at least 1 therapy (Subprotocol A) or 2 immunosuppressive therapies (Subprotocol B Subgroup 1) at the maximally tolerated doses as recommended by theKidney Disease: Improving Global Outcomes (KDIGO) guidelines (KDIGO, 2024).Inadequate response is defined as: UPCR ≥ 1.0 mg/mg.

• Subprotocol B (Subgroup 2): Refractory SLE participants with inadequate response tomultiple therapies (excluding hydroxychloroquine or corticosteroids) and have failedeither a biologic agent or cyclophosphamide.

• Subprotocol B (Part B Subgroup 2): British Isles Lupus Assessment Group (BILAG)-2004level A disease in 1 organ system or BILAG-2004 level B disease in ≥ 2 organ systems

• Subprotocol B (Part B Subgroup 2): Physician Global Assessment (PGA) ≥ 1

• Subprotocol A and B: If receiving any of the following medications, participantsmust be on these doses prior to Day 1:

1. Prednisone dose ≤ 20 mg/day (or its equivalent in other corticosteroid forms)and at a stable dose for 5 days

2. Hydroxychloroquine dose ≤ 400 mg/day and at a stable dose for 4 weeks. Otherequivalent antimalarials (chloroquine, quinacrine) are also accepted at astable dose for 4 weeks.

3. MMF dose ≤ 3 g/day or MPA dose ≤ 2160 mg/day and at a stable dose for 2 weeks.

4. AZA dose ≤ 2 mg/kg/day and at a stable dose for 2 weeks.

5. Methotrexate > 25 mg/week and at a stable dose for 2 weeks

6. Leflunomide > 20 mg/day and at a stable dose for 2 weeks

7. Dapsone > 300 mg/day and at a stable dose for 2 weeks.

• Subprotocol C (Part A and Part B): Diagnosis of RA according to the 2010ACR/European Alliance of Associations for Rheumatology (EULAR) classificationcriteria.

• Subprotocol C (Part A and Part B): Moderate to severe disease activity as defined byDAS28-CRP > 3.2 with ≥ 3 swollen joints and ≥ 3 tender joints (based on 28 jointcounts) at screening.

• Subprotocol C (Part A and Part B): Refractory disease defined as:

• Active disease despite having received treatment with:

1. at least 1 conventional synthetic disease-modifying antirheumatic drug (csDMARD), AND

2. at least 2 biologic disease-modifying antirheumatic drugs (bDMARDs) ofdifferent mechanisms of action OR 1 bDMARD and at least 1 targeted syntheticdisease-modifying antirheumatic drugs (tsDMARD).

• Inadequate response or intolerance to csDMARDs, bDMARDs, and tsDMARDs should bedefined as:

1. Participant having active disease despite a minimum of 12 weeks of treatmentwith a csDMARD, bDMARD, or tsDMARD.

2. Intolerance to treatment as defined by participant having experienced anadverse effect from treatment with a csDMARD, bDMARD, or tsDMARD.

• Subprotocol C (Part B): High sensitivity C-Reactive Protein (hsCRP) level ≥ upperlimit of normal per the central laboratory at screening.

Exclusion Criteria:

• Subprotocol A, B and C: Receipt of a live and/or live attenuated vaccine within 4weeks prior to first dose of trial drug, during the treatment period, or untilB-cell repletion after the end of the treatment period. Administration ofinactivated (killed) vaccines is acceptable.

• Subprotocol A and B: Estimated glomerular filtration rate (eGFR) of < 30 mL perminute per 1.73 m^2 of body surface area (calculated using the Modification of Dietin Renal Disease [MDRD] formula, with screening laboratory results for serumcreatinine value).

• Subprotocol A and B: Significant likely irreversible organ damage related to SLE (eg, end-stage renal disease [ESRD]).

• Subprotocol A and B: Any acute, severe lupus related flare during screening thatneeds immediate treatment.

• Subprotocol A and B: A previous kidney transplant or planned transplant within trialtreatment period.

• Subprotocol A and B: History of or current renal diseases (Parts A and B, Subgroup

1. that in the opinion of the investigator could interfere with the LN assessmentand confound the disease activity assessment (eg, diabetic nephropathy).

• Subprotocol A: Renal biopsy showing pure class V.

• Subprotocol B: Active CNS Lupus within one year prior to screening.

• Subprotocol B and C: History or presence of clinically relevant central nervoussystem (CNS) pathology or event such as seizure, paresis, aphasia, stroke, severebrain injuries, dementia, Parkinson's disease, cerebellar disease, or organic brainsyndrome.

• Subprotocol C: Prior history of current inflammatory joint disease other than RAincluding but not limited to SLE, mixed connective tissue disorder, scleroderma,polymyositis, or significant systemic involvement secondary to RA (eg, vasculitis,pulmonary fibrosis, or Felty's syndrome).

• Subprotocol C: Functional Class IV as defined by the ACR classification offunctional status in RA.

• Subprotocol A, B and C: Receipt of the following medications or treatments at anytime prior to Day 1:

1. B-cell directed CAR T-cell and T-cell engager therapies

2. Total lymphoid irradiation

3. Bone marrow transplant

4. T-cell vaccination therapy

5. Natalizumab