SG301-SC Injection Safety Study in Subjects With Systemic Lupus Erythematosus

Inclusion Criteria:

Part A (healthy volunteers)

1. Male healthy adults aged 18-50 years (inclusive);

2. Male participants weighed 50-100 kg (inclusive) with the body mass index of 19.0-27.0 kg/m2 (inclusive);

3. Participants whose partners are of childbearing potential must agree to useeffective contraceptive methods throughout the study period and for 6 monthsfollowing the last dose.

Part B (SLE participants)

1. Males or females aged 18-65 years (inclusive);

2. BMI 18.5-30.0 kg/m2 (inclusive);

3. Have diagnosed as SLE based on the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) SLE classification criteria, withinadequate response or intolerance to or having relapsed despite the standardtreatment;

4. SELENA-SLEDAI score >4 and ≤12;

5. Serologically ANA and/or anti-ds-DNA antibody tested positive;

6. Having received a standard treatment for at least 12 weeks prior to the first dosethat has remained at a stable dose for at least 4 weeks prior to the first dose;

7. Laboratory values at screening meets the following criteria:

8. Liver function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2ULN, total bilirubin <1.5×ULN;

9. Renal function: creatinine (Cr) and urea ≤1.5×ULN; eGFR >60 ml/min (calculatedby the MDRD formula); urine total protein-creatinine ratio ≤3.0 g/g or 24hurine protein ≤3.5 g;

10. Bone marrow function: Hb≥100g/L, WBC≥3.0×109/L, PLT≥75×109/L;

11. Participants who are of childbearing potential or whose partners are ofchildbearing potential must agree to use effective contraceptive methodsthroughout the study period and for 6 months following the last dose.

Exclusion Criteria:

Part A (healthy volunteers)

1. Have a history of allergies or likely to be allergic to the investigational drug orany of their ingredients judged by the investigators;

2. Have previously received drugs of the same target (CD38);

3. Have participated in a clinical trial of any drug or medical device within 3 monthsor 5 half-lives prior to dosing, whichever is longer;

4. Have received any prescription drugs or Chinese herbal medicines within 4 weeksprior to dosing, or any non-prescription or dietary supplements within 2 weeks priorto dosing;

5. Have infections within 2 weeks prior to first dose (including but not limited toviral, bacterial, or fungal infections);

6. Have experienced symptomatic herpes zoster within 3 months prior to dosing;

7. Presence of any of the following diseases assessed by the investigator as abnormalwith clinical significance within 6 months prior to dosing;

8. Have a history of cardiovascular diseases within 6 months prior to dosing: chroniccongestive heart failure (New York Heart Association [NYHA] Class III or IV),myocardial infarction, severe heart diseases (e.g., unstable angina, cardiogenicshock, arrhythmias requiring treatment, heart valve diseases, hypertrophiccardiomyopathy, and rheumatic heart disease, etc.), and familial long QT intervalsyndrome, etc.;

9. Presence of chronic nervous system symptoms such as dizziness and headache prior todosing;

10. Blood cell count below the lower limit of normal (LLN), or clinically significantabnormalities in any other hematology tests within 1 week prior to dosing;

11. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >1.2×ULN, totalbilirubin >1.2×ULN;

12. ECG abnormalities with clinical significance, e.g. QTcF >450 ms;

13. Any vital signs abnormal with clinical significance;

14. Fasting blood glucose above ULN;

15. Any abnormal from physical examination, laboratory tests, or chest CT with clinicalsignificance;

16. Hepatitis B surface antigen (HBsAg) or core antibody (HBcAb) positive, hepatitis Cvirus (HCV) antibody positive, TPPA positive, or HIV antibody positive;

17. Mycobacterium tuberculosis infection;

18. Having received a live or attenuated live vaccine within 4 weeks prior to dosing orplanning to do so during the trial;

19. Skin injection site abnormal, including but not limited to birthmarks, scars, blackmoles, tattoos, and open wounds;

20. Blood donation ≥400 ml or blood loss ≥400 ml within 4 weeks prior to dosing, orhaving received blood transfusion within 8 weeks prior to dosing;

21. A history of heavy drinking within 3 months prior to dosing;

22. A history of drug abuse within 5 years prior to dosing or use of narcotics within 3months prior to the trial.

Part B (SLE participants)

1. Has a history of central nervous system disorders that require prohibited medicinetreatment within 2 months prior to the first dose;

2. Presence of concomitant rheumatic diseases within 12 months prior to the first dose,including but not limited to rheumatoid arthritis, spondyloarthritis,dermatomyositis/polymyositis, Sjogren's syndrome, systemic sclerosis, mixedconnective tissue disease, and overlap syndrome, etc.;

3. Presence of catastrophic antiphospholipid syndrome within 12 months prior to thefirst dose;

4. Has a history of non-SLE inflammatory skin or joint disease within 12 months priorto the first dose;

5. Presence of chronic active infection or acute infection within 4 weeks prior tofirst dose or superficial skin infection within 1 week prior to first dose;

6. A known or suspected history of immunosuppression;

7. Have undergone a major surgery within 12 weeks prior to the first dose or having anunhealed wound, ulcer or fracture, or planning to undergo a major surgery during thestudy;

8. Having participated in any clinical trial within 12 weeks prior to the first dose orhave received other investigational products within 5 half-live, whichever islonger;

9. Have received any drugs targeting T or B lymphocytes (e.g., rituximab) within 6months or cytokines or cytokines receptors (e.g., belimumab, telitacicept, etc.)treatment within 5 half-lives prior to the first dose;

10. Having received JAK inhibitors treatment within 12 weeks or 5 half-lives prior tothe first dose, whichever is shorter;

11. Having received any of the following treatment within 12 weeks prior to the firstdose:

12. Intravenous immunoglobulin (IVIG)

13. Plasma exchange

14. Intravenous cyclophosphamide;

15. Have diseases with major clinical significance within 6 months prior to first dose,including but not limited to circulatory system disorders, endocrine systemdisorders, nervous system disorders, blood system disorders, immune systemdisorders, and psychiatric disorders, etc.;

16. A history of cardiovascular diseases within 6 months prior to the first dose,including but not limited to chronic congestive heart failure (NYHA Class III orIV), myocardial infarction, severe heart diseases (e.g., unstable angina,cardiogenic shock, arrhythmias requiring treatment, heart valve diseases,hypertrophic cardiomyopathy, and rheumatic heart disease, etc.), QTcF >450 ms orfamilial long QT interval syndrome, poorly controlled hypertension;

17. Mycobacterium tuberculosis infection;

18. Presence of active hepatitis:

19. HBsAg positive and/or HBcAb positive and HBV DNA positive;

20. HCV antibody positive and HCV RNA positive;

21. HIV antibody positive;

22. Both TPPA and RPR positive;

23. Known allergy to monoclonal antibody drugs or to any excipient of theinvestigational drug;

24. Having received a live or attenuated live vaccine within 4 weeks prior to the firstdose or planning to do so during the study;

25. Have a history of major organ transplantation or hematopoietic stem cell/ bonemarrow transplantation;

26. Have a history of malignancy within 5 years prior to first dose;

27. Participants with depression or suicidal tendency;

28. Have a history of heavy drinking or drug abuse within 3 months prior to first dose;

29. Pregnant or breastfeeding women, or women who plan to become pregnant or maybreastfeed during the study and for 6 months following the last dose; maleparticipants whose partner plans to become pregnant during the study.