EncompaSSc: Evaluation of MTX-474 in Participants With Diffuse Cutaneous Systemic Sclerosis (dcSSc)

Inclusion Criteria: 1. Diagnosis of diffuse cutaneous systemic sclerosis, classified according to 2013 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2. Participant is either: 1. Within 2 years of their first non-Raynaud's symptom and their mRSS is \>7; OR 2. \>2 and ≤5 years from their first non-Raynaud's symptom, their mRSS is between 10 and 30, they are negative for the RNA polymerase 3 autoantibody, and (1) they have never had any previous spontaneous improvement in skin thickening of ≥4 points by mRSS on exams performed by the same clinician, or (2) they were never clinically noted to have a meaningful spontaneous reduction in skin thickness if mRSS was never done; OR 3. \>5 and ≤10 years from their first non-Raynaud's symptom, their mRSS is between \>15 and ≤25, they are negative for the RNA polymerase 3 autoantibody, and (1) they have never had any previous spontaneous improvement in skin thickening of ≥4 points by mRSS, or (2) were never clinically noted to have a meaningful spontaneous reduction in skin thickness if mRSS was never done. 3. Participant is ≥18 years of age at time of signing the ICF. 4. Able to understand the study and provide a signed, written ICF 5. Able to read and understand the language of the ICF and other study-related materials 6. Forced vital capacity (FVCpp) of ≥45 pp10 7. Have diffusing capacity of the lungs for carbon monoxide (DLCO) of ≥30 percent predicted at Screening 8. Willing and able to complete all protocol-required study visits and procedures 9. Participants of childbearing potential must have a negative serum pregnancy test at Screening. 10. All participants with reproductive potential must agree to use and follow medically approved, highly effective methods of contraception during treatment and until 5 half-lives or 125 days after the last dose, whichever is longer Exclusion Criteria: 1. Concomitantly have another serious medical illness, which, in the opinion of the Investigator, would interfere with the participant's ability to complete the study 2. Participant is currently on immunosuppressive therapy, systemic glucocorticoids or other antifibrotic agents detailed as follows: 1. Immunosuppresive agents: Cyclophosphamide (IV or oral if used in the 6 months prior to Screening), calcineurin inhibitors (if used in the 30 days prior to Screening), azathioprine (if used in the 30 days prior to Screening), Janus-kinase inhibitors (if used in the 30 days prior to Screening), rituximab (if used in the 6 months prior to Screening), tocilizumab (if used in the 60 days prior to Screening) or any other biologic Disease-Modifying Antirheumatic Drugs (DMARD, if used in the last 30 days or 3 half-lives prior to Screening, whichever is longer) 2. Antifibrotic agents: nintedanib or pirfenidone (if used in the 30 days prior to Screening). Also, exclusionary if used within 3 months of Screening are tyrosine-kinase inhibitors with recognized anti-fibrotic activity (imatinib, nilotinib, etc.) 3. Systemic glucocorticoids: equivalent doses of prednisone greater than 10 mg/day (≤10 mg/day allowed). Has received any pulse intramuscular (IM) or intravenous (IV) steroid within 1 month of Screening 4. Other agents: i. mycophenolate mofetil unless on a stable dose for at least 6 months prior to Screening and there are no plans to adjust the dose during the study; ii. mycophenolic acid unless on a stable dose for at least 6 months prior to Screening and there are no plans to adjust the dose during the study; iii. hydroxychloroquine unless on a stable dose for at least 3 months prior to Screening and there are no plans to adjust the dose during the study; and iv. methotrexate unless on a stable dose for at least 3 months prior to Screening and there are no plans to adjust the dose during the study. 3. Previous or planned hematopoietic stem cell or solid organ transplantation 4. Previous treatment with chimeric antigen receptor (CAR)-T/CAR-NK therapy 5. Clinically significant PAH as determined by the Investigator at, or prior to first day of dosing (Baseline) 6. Current use of PAH medication (endothelin receptor antagonists, prostacyclin analogues, soluble guanylate cyclase stimulators) excluding calcium channel blockers and phosphodiesterase-5 inhibitors 7. Pregnant or currently breastfeeding 8. Aspartate transaminase (AST) or alanine transaminase (ALT) \>2.0 upper limit of normal 9. Creatinine clearance \<45mL/min 10. History of myocardial infarction, angina or congestive heart failure 11. International normalized ratio \>2 or partial thromboplastin time \>1.5 × upper limit of normal 12. Active infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C 13. History of clinically significant thrombotic event within 12 months prior to Screening 14. Positive anticentromere antibody 15. Systemic sclerosis renal crisis within 12 months prior to Screening 16. Confirmed diagnosis of overlap syndrome, systemic lupus erythematosus with anti-double strand (ds)DNA antibody, rheumatoid arthritis with anti-cyclic citrullinated peptide (anti-CCP) antibody, or systemic sclerosis mimics (eosinophilic fasciitis, scleromyxedema) at the time of inclusion in the study 17. Known malignancy or history of malignancy within 5 years of Screening other than non-melanoma skin cancer and in situ cervical cancer 18. Major surgery within 8 weeks prior to Screening or planned surgery during study period 19. Unable to routinely access veins for blood draws and IV infusions 20. Currently receiving another experimental agent or participating in another clinical trial. If a participant has recently received another experimental agent, then the last dose must have been at least 5 half-lives or 30 days (whichever is longer) prior to Screening 21. History of myocardial infarction, angina or congestive heart failure