Phase 2 Study of ALXN2050 in Proliferative Lupus Nephritis (LN) or Immunoglobulin A Nephropathy (IgAN)

Lab values

• Both Cohorts: • eGFR ≤ 30 milliliters/minute/1.73 squared meters during Screening calculated by Chronic Kidney Disease Epidemiology Collaboration. • For participants with eGFR < 45 mL/min/1.73 m2 at Screening, presence of any of the following in glomeruli on most recent kidney biopsy prior to or during the Screening Period: a. ≥ 50% interstitial fibrosis and tubular atrophy b. ≥ 50% glomerular sclerosis c. ≥ 50% active crescent formation • Concomitant significant renal disease other than LN or IgAN on the most recent biopsy prior to or during the Screening Period. • History of solid organ or bone marrow transplant, or planned transplant during the Blinded Extended Treatment Period (50 weeks). • Splenectomy or functional asplenia. • Known or suspected complement deficiency, unless attributable to underlying disease (that is, LN and IgAN). • Bone marrow insufficiency with absolute neutrophil count < 1.3 × 10^3/microliter; thrombocytopenia (platelet count < 50,000/cubic millimeter). For LN Cohort: • Participants who have initiated any of the following treatments for the current active LN flare: a. Cyclophosphamide ≤ 6 months prior to Screening b. CNIs ≤ 1 month prior to Screening c. A cumulative dose of intravenous (IV) methylprednisolone > 3 g d. Mycophenolate mofetil > 2 g/day (or equivalent) for ≥ 8 consecutive weeks prior to Screening e. Prednisone or prednisone equivalent ≥ 0.5 mg/kg/day for ≥ 8 consecutive weeks prior to Screening • Uncontrolled hypertension (systolic blood pressure > 160 mmHg or diastolic blood pressure > 110 mmHg) on 2 or more measurements during the Screening Period. For IgAN Cohort: • Diagnosis of rapid progressive glomerulonephritis as measured by eGFR loss ≥ 30% over a period of 3 months prior to or during the Screening Period. • Secondary etiologies of IgAN. • Clinically active Henoch-Schonlein purpura (IgA vasculitis) requiring treatment • Prednisone or prednisone equivalent > 20 mg/day for > 14 consecutive days or any other systemic immunosuppression for the treatment of IgAN ≤ 6 months prior to Screening • Blood pressure of ≥ 140/90 mmHg during the Screening Period confirmed on 2 measures > 30 minutes apart. • Body mass index ≥ 38 kg/m2 during Screening

• LN Cohort • Clinical diagnosis of SLE by 2019 American College of Rheumatology and European League Against Rheumatism criteria. • Diagnosis of 2018 Revised International Society of Nephrology/Renal Pathology Society classification (active focal or diffuse proliferative LN Class III or IV) confirmed by biopsy obtained ≤ 6 months prior to Screening or during Screening Period. Participants may co-exhibit Class V disease. Participants with de novo or relapsing disease may be eligible. • Clinically active LN at Screening requiring/receiving immunosuppression induction treatment in the opinion of the Investigator. • Proteinuria with UPCR ≥ 1 g/g based on one 24 hour urine collection during the Screening Period. IgAN Cohort • Established diagnosis of primary IgAN based on kidney biopsy obtained any time prior to or during the Screening Period. • Mean proteinuria ≥ 1 g/day on 2 complete and valid 24 hour urine collections during the Screening Period. • For participants with a kidney biopsy performed > 1 year prior to Screening that was used for eligibility: Presence of hematuria as defined by a positive result for blood on urine dipstick or ≥ 10 red blood cells (RBCs)/high power field (hpf) microscopy on urine sediment (documented by the local laboratory) during Screening Period. Presence of hematuria documented by the central laboratory may also be acceptable. • Compliance with stable and optimal dose of RAS inhibitor treatment including maximum allowed or tolerated ACE inhibitor and/or ARB dose for ≥ 3 months prior to Screening with no expected change in dose during the Blinded Treatment Periods (through Week 50) (participants with established intolerance to RAS inhibitors may be included). • Controlled and stable blood pressure (defined as < 140/90 millimeters of mercury [mmHg]) over the past 3 months prior to randomization