Study of Daxdilimab (HZN-7734) in Participants With Active Proliferative Lupus Nephritis (LN)

Inclusion Criteria:

• Willing and able to understand and provide written informed consent

• Adult men or women 18 to 80 years of age

• Willing and able to comply with the prescribed treatment protocol and evaluationsfor the duration of the trial

• Fulfill the 2019 European League Against Rheumatism/American College of RheumatologyClassification Criteria for Systemic Lupus Erythematosus (SLE)

• Have at least one of the following at Screening per central lab:

• Antinuclear antibodies (ANA) ≥ 1:80

• Anti-dsDNA antibodies elevated to above normal range as established by thecentral laboratory (ie, positive results)

• Anti-Smith antibodies elevated to above normal (ie, positive results).

• Diagnosis of proliferative LN based on a renal biopsy obtained within 6 months priorto signing the informed consent form (ICF) or during the Screening Period:

• Class III (± class V) or class IV (± class V) LN according to the World HealthOrganization (WHO) or 2003 International Society of Nephrology (ISN)/RenalPathology Society (RPS) classification (based on local evaluation of renalbiopsy).

• Urine protein to creatinine ratio ≥113.17 mg/mmol, obtained via a 24-hour urinecollection at Screening.

• Estimated glomerular filtration rate ≥35 mL/min/1.73 m2

• Negative serum beta-human chorionic gonadotropin test at Screening (females ofchildbearing potential only).

Key Exclusion Criteria:

• History of allergy, hypersensitivity reaction, or anaphylaxis to any component ofthe investigational product or to a previous monoclonal antibody or humanimmunoglobulin therapy.

• Known intolerance to ≤1.0 gm/day of MMF or equivalent dose of mycophenolic acid (MPA).

• A diagnosis of pure Class V membranous LN based on a renal biopsy obtained within 6months prior to signing ICF or during the Screening Period.

• History of dialysis within 12 months prior to signing the ICF or expected need forrenal replacement therapy (dialysis or renal transplant) within a 12-month periodafter enrollment.

• History of, or current renal diseases (other than LN) that in the opinion of theInvestigator could interfere with the LN assessment and confound the diseaseactivity assessment (eg, diabetic nephropathy).

• Known history of a primary immunodeficiency or an underlying condition such as knownhuman immunodeficiency virus (HIV) infection, a positive result for HIV infectionper central laboratory, splenectomy, or any underlying condition that in the opinionof the Investigator significantly predisposes the participant to infection.

• Hepatitis B, Hepatitis C, active tuberculosis (TB), any severe herpes infection,clinically active infection, or opportunistic infection.

• Clinically significant cardiac disease including unstable angina, myocardialinfarction, congestive heart failure within 6 months prior to Randomization.

• History of cancer within the past 5 years, except in situ carcinoma of the cervix,cutaneous basal cell or squamous cell carcinoma with curative therapy.

• Receipt of a live vaccine within 4 weeks prior to Day 1.

• The use of immunosuppressants, biologics, and DMARDS within the protocol definedwashout periods.