Evaluation of Safety, Pharmacokinetics and Pharmacodynamics of Arnovie101, an mRNA-LNP-Based In Vivo CAR-T Therapy, for the Treatment of B Cell-Mediated Autoimmune Diseases (SLE and AIHA)

1. Presence of an unresected thymoma.

2. Pregnant or lactating women.

3. History of active severe or unstable neuropsychiatric SLE, including but not limited to poorly controlled seizures, psychosis, acute confusional state, cerebrovascular accident, demyelinating syndrome, cranial neuropathy, or active central nervous system vasculitis.

4. Presence of clinically significant central nervous system disease or pathology before screening, including but not limited to: cerebrovascular accident, aneurysm, epilepsy, convulsions/seizures, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis.

5. History of major organ transplantation (e.g., heart, lung, kidney, liver) or hematopoietic stem cell/bone marrow transplantation.

6. Presence of known active infection at screening, including active tuberculosis, active or infectious pneumonia, or recurrent peptic ulcer; requiring hospitalization, intravenous antibiotics within 4 weeks before screening, or oral antibiotics within 2 weeks before screening; history of herpes zoster within 12 weeks before screening; history of human immunodeficiency virus (HIV) or positive HIV antibody test; positive hepatitis B surface antigen (HBsAg) and/or positive anti-hepatitis B core antibody (HBcAb) with detectable hepatitis B virus (HBV) DNA above the lower limit of detection; positive hepatitis C virus (HCV) antibody with detectable HCV RNA above the lower limit of detection; positive syphilis antibody with active infection.

7. History of any of the following cardiovascular diseases within 6 months before screening: New York Heart Association (NYHA) class II or higher heart failure, myocardial infarction, unstable angina, uncontrolled or symptomatic atrial arrhythmias (e.g., second-degree type II atrioventricular block, third-degree atrioventricular block, symptomatic bradycardia with ventricular rate \<50 bpm), any ventricular arrhythmia, or other clinically significant heart disease. QTcF \>480 ms (Fridericia's formula), left ventricular ejection fraction (LVEF) \<50% by echocardiography at screening, or other significant electrocardiogram abnormalities.

8. Malignancy within 5 years before signing the ICF, except for: curatively treated basal cell carcinoma of the skin, superficial bladder cancer, localized prostate cancer, biopsy-proven cervical carcinoma in situ or cervical squamous intraepithelial lesion detected by Pap smear, and completely resected ductal carcinoma in situ of the breast.

9. Previous treatment with B-cell targeted therapies such as belimumab, rituximab, telitacicept; anti-CD22 agents (e.g., epratuzumab); anti-CD52 agents (e.g., alemtuzumab), or other similar biologics; TNF-α antagonists, IL-6 antagonists, IL-1 antagonists, selective T-cell costimulation modulators, etc., with less than 5 half-lives before screening.

10. Use of any other investigational drug for SLE in a clinical trial within 4 weeks before screening.

11. Presence of other serious diseases, including liver disease, neurological/psychiatric disorders, endocrine system disorders, hematological disorders (including moderate-to-severe dyslipidemia and related conditions), which in the investigator's judgment would affect participation in this study.

12. Receipt of non-biologic investigational drugs (e.g., BTK inhibitors, JAK inhibitors), intravenous immunoglobulin, or plasma exchange within 4 weeks or 5 half-lives (whichever is shorter) before screening.

13. Vaccination within 30 days before the first dose of study drug.

14. Prior treatment with mRNA-LNP or other LNP-based drugs within 2 years before the first dose of study drug.

15. History of asthma, severe allergic reactions, or known allergy to any active or inactive ingredient of the study drug (including background therapy).

16. Prior CAR-T cell therapy.

17. Major surgery within 4 weeks before the first dose of study drug, or minor surgery within 2 weeks before the first dose.

18. Severe mental disorder or suicidal tendency.

19. Any other condition that, in the investigator's judgment, makes the participant unsuitable for this study.

What this study is about