A Study of LY4298445 in Healthy Participants and Participants With Systemic Lupus Erythematosus (SLE) or Rheumatoid Arthritis (RA)

Prior treatment

• Have active central nervous system lupus as defined by ACR nomenclature for neuropsychiatric lupus syndromes and as captured by Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K); seizure, psychosis, organic brain syndrome, visual disturbance, cranial nerve disorder, lupus headache, and cerebrovascular accident, within 2 months prior to screening

Other illness

• Have known allergies to LY4298445, related compounds, or any components of the formulation

Lab values

• Have severe active lupus-associated renal disease (lupus nephritis) defined clinically and/or by
  • urine protein/creatinine ratio greater than 200 milligrams per millimole (mg/mmol) (as an estimate of approximate proteinuria greater than 2 reams (g) per day) or
  • an estimated glomerular filtration rate (eGFR) less than 40 milliliters per minute (mL/min)/1.73 m² at screening, as calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) 2021.
  • requiring hemodialysis within 6 months prior to screening

Other

• Are individuals assigned female at birth (AFAB) who are lactating or have a positive pregnancy test at screening or Day -1.
• Have a Class 4 RA according to the ACR revised criteria

• Healthy participants between the ages of 18 and 55 years.
• Have body weight of at least 50 kilograms (kg) and body mass index (BMI) between 18 and 32 kilogram per square meter (kg/m²), inclusive.
  • Participants with Systemic Lupus Erythematosus (SLE)
• Are 18 to 75 years of age, inclusive.
• Have body weight between 45 and 145 kg, inclusive, and BMI between 18 and 35 kg/m², inclusive.
• Have a clinical diagnosis of SLE according to the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria at least 6 months prior to screening.
  • Participants with Rheumatoid Arthritis (RA)
• Are 18 to 75 years of age, inclusive.
• Have body weight between 45 and 145 kg, inclusive, and BMI between 18 and 35 kg/m², inclusive.
• Have a diagnosis of adult-onset RA for at least 6 months prior to screening, as defined by the 2010 ACR/EULAR classification criteria
• Have Disease Activity Score in 28 joints (DAS28)-high-sensitivity C-reactive protein (hsCRP) greater than or equal to 3.2.
• Have positive test results for rheumatoid factor or anti-citrullinated peptide antibodies
• Have had a history of failure (an inadequate response, intolerance, or loss of response) to at least 2 advanced therapies (biological disease-modifying antirheumatic drug \[bDMARD\] or targeted synthetic DMARD \[tsDMARD\]) after failing a conventional synthetic DMARD (csDMARD).