MTS109 in Patients With Refractory Autoimmune Diseases

Exclusion Criteria1

• SLE subjects: a) Drug-induced SLE; b) Subjects with lupus crisis, or who require medications prohibited by the protocol due to comorbidities, or who are considered ineligible by the investigator. 2) IIM subjects: a) Subjects with documented inclusion body myositis (IBM), drug-induced PM or DM, malignancy-associated PM or DM, or non-inflammatory myopathy (e.g., muscular dystrophy); b) Uncontrolled extramuscular involvement related to PM or DM: ILD: FVC <55% or requiring oxygen therapy (FVC ≥55% to be evaluated for eligibility by the lead investigator); Severe dysphagia that, in the investigator's judgment, would increase subject risk by participating in the clinical trial; Severe cardiac manifestations (e.g., congestive heart failure, arrhythmia, treatable conduction abnormality, or myocardial infarction) that, in the investigator's judgment, would increase subject risk by participating in the clinical trial. 3) SSc subjects: a) Uncontrolled severe pulmonary arterial hypertension (PAH) related to SSc; b) Rapidly progressive lower gastrointestinal tract (small and large intestine) involvement related to SSc requiring parenteral nutrition; active gastric antral vascular ectasia; c) Uncontrolled or rapidly progressive ILD with oxygen saturation (SaO2) <92% on room air; or requiring mechanical ventilatory support within 1 year prior to signing informed consent. 4) AAV subjects: a) Crescentic glomerulonephritis, acute polyneuritis, or central nervous system (CNS) involvement other than AAV at screening; b) Life-threatening severe vasculitis (including diffuse alveolar hemorrhage, respiratory failure, intestinal perforation or massive bleeding, cerebral vasculitis, cardiac vasculitis, etc.); c) Secondary vasculitis (e.g., SLE, Henoch-Schönlein purpura, drug-induced, malignancy-associated, infection-induced, primary immunodeficiency, etc.). 5) SS subjects: a) Poorly controlled severe systemic primary Sjögren's syndrome (pSS) manifestations at baseline that, in the investigator's assessment, may place the subject at excessive risk; b) Secondary Sjögren's syndrome with other confirmed autoimmune diseases (e.g., rheumatoid arthritis, SLE, scleroderma, inflammatory bowel disease); c) Subjects requiring regular use of medications known to cause dry mouth/dry eye as common major side effects; d) Subjects with other diseases that may interfere with efficacy assessment of primary Sjögren's syndrome, such as inflammatory bowel disease, gout, sarcoidosis, amyloidosis, IgG4-related disease, etc. All subjects: 6) Subjects with a history of severe hypersensitivity or anaphylaxis; 7) Subjects with contraindications or hypersensitivity to any component of the investigational product; 8) Subjects with any of the following cardiac diseases: a) New York Heart Association (NYHA) Class III or IV congestive heart failure; b) Myocardial infarction or coronary artery bypass grafting within 6 months prior to screening; c) Clinically significant ventricular arrhythmia at screening, history of unexplained syncope not due to vasovagal reaction or dehydration, corrected QT interval (QTc) >480 ms, or history of severe non-ischemic cardiomyopathy; 9) Subjects with any active malignancy or history of malignancy within 5 years prior to screening, excluding: early-stage tumors treated with curative intent (carcinoma in situ or Stage I tumor, non-ulcerated primary melanoma <1 mm depth without lymph node involvement), basal cell carcinoma of the skin, squamous cell carcinoma of the skin, cervical carcinoma in situ, or breast carcinoma in situ treated with potentially curative therapy; 10) Subjects with any other known autoimmune disease other than the study disease; 11) Subjects requiring long-term use of anticoagulants affecting coagulation function; 12) Subjects with clinically significant bleeding symptoms or obvious bleeding tendency within 6 months prior to screening, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, etc.; hereditary or acquired bleeding and thrombotic tendency (e.g., hemophilia, coagulopathy, hypersplenism, etc.); subjects with arterial or venous thrombotic events within 6 months prior to screening, such as cerebrovascular disease (including cerebral hemorrhage, cerebral infarction, etc.), deep vein thrombosis and/or pulmonary embolism; 13) Subjects with any severe underlying disease at screening, e.g.: a) Evidence of uncontrolled infection or viral, bacterial, fungal, or other infection treated with systemic intravenous antibiotics; b) Evidence of clinically significant dementia or altered mental status; c) History of any other central nervous system disease or neurodegenerative disease, such as epilepsy, seizure, paralysis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, psychosis; 14) Subjects with positive screening results for any of the following: a) Positive human immunodeficiency virus (HIV) antibody; b) Positive hepatitis B surface antigen (HBsAg); or positive hepatitis B core antibody (HBcAb) with HBV-DNA above the lower limit of detection of the assay; c) Positive hepatitis C virus (HCV) antibody with HCV RNA above the lower limit of detection of the assay; d) Active syphilis (excluding false-positive due to disease); 15) Subjects with positive plasma cytomegalovirus (CMV) DNA or plasma Epstein-Barr virus (EBV) DNA (viral active); 16) Subjects with active tuberculosis or untreated latent tuberculosis prior to screening; 17) Subjects who received other investigational drugs within 4 weeks prior to signing informed consent form (ICF), or for whom the time from the last dose of a previous investigational drug to the date of signing ICF is less than 5 elimination half-lives of that drug (whichever is longer); 18) Subjects who received plasmapheresis or immunoadsorption therapy within 4 weeks prior to dosing; 19) Subjects who received B-cell targeted therapy within 6 months prior to dosing, including but not limited to belimumab, telitacicept, etc.; 20) Subjects who received biologic therapy such as anti-TNF-α antibody within 12 weeks prior to dosing; 21) Subjects who received tacrolimus, cyclosporine, azathioprine, mycophenolate mofetil, mycophenolic acid, methotrexate, etc., within 2 weeks prior to dosing; 22) Subjects who received neonatal Fc receptor (FcRn) antagonist therapy (e.g., efgartigimod) within 3 weeks prior to dosing; 23) Subjects who received complement inhibition therapy (e.g., eculizumab) within 3 weeks prior to dosing; 24) Subjects who received live attenuated vaccine or mRNA vaccine within 8 weeks prior to enrollment, or inactivated vaccine within 2 weeks prior to enrollment; 25) Subjects who underwent major surgery within 8 weeks prior to screening or plan to undergo surgery during the study; 26) Subjects with a history of organ/bone marrow/peripheral blood/umbilical cord blood transplantation; 27) Subjects who previously received CAR-T product therapy targeting any target; 28) Subjects with any condition that, in the investigator's judgment, may prevent completion of the entire study, interfere with study results, or make participation in the study not in the subject's best interest.