Inclusion Criteria:
1. Greater than or equal to 18 years of age
2. Able to understand key components of the study as described in the written informed consent document and willing and able to provide written informed consent.
3. If female, surgically sterile (post hysterectomy, bilateral salpingectomy, or bilateral oophorectomy), postmenopausal (greater than 12 months of amenorrhea without alternative medical causes), or, if of childbearing potential, is using a highly effective contraception until 90 days after EOS visit.
4. If male, is vasectomized, has undergone bilateral orchidectomy, agrees to abstinence of heterosexual intercourse, or only has female partner using highly effective contraception, surgically sterile or postmenopausal and agrees to use method until 90 days after EOS visit.
5. Receiving kidney allograft from deceased donor or non-human leukocyte antigen (HLA) identical living donor.
a) Repeat kidney transplant allowed if no previous kidney transplant(s) failed due to recurrent disease within first year, acute rejection or nonsurgical thrombosis
6. Able \& willing to comply with all study procedures, including PK and PD assessments, as assessed by the Investigator
7. Vaccination up to date per the center's SOC as assessed by the Investigator.
8. In the opinion of the Investigator, is able to adhere to the study requirements.
Exclusion Criteria:
1. Negative for EBV or Epstein-Barr nuclear antigen antibody
2. Know allergy to study medication (rATG, corticosteroids, MMF, tacrolimus, or VEL-101) or its components or a history of a severe allergic reaction to any drug.
3. History of previous non-kidney solid organ, vascular composite allograft, pancreatic islet, stem cell or bone marrow transplant.
4. Planned multiorgan transplant, including dual or en-bloc kidney transplant
5. Anticipated cold ischemia time (CIT) \>30 hours
6. Donor with Kidney Donor Profile Index (KDPI) \> 85%
7. Panel reactive antibody \>80%, calculated panel-reactive antibody (CPRA)\>80% or history of HLA desensitization
8. Positive T or B cell flow, cytotoxic, or virtual crossmatch at Screening
9. Current or historical DSA
10. Recipient or donor with positive hepatitis B surface antigen (HBsAG), hepatitis B core antibody (HBcAb), hepatitis B virus (HBV) nucleic acid testing (NAT), hepatitis C virus (HCV) antibody, HCV NAT, human immunodeficiency virus (HIV), or HIV NAT
11. Recipient who is CMV IgG negative (R-) receiving a kidney from a donor who is CMV IgG positive (D+)
12. Thrombocytopenia (platelets \< 75,00/mm3), leukopenia (white blood cells \[WBC\] \<3,000/mm3), or anemia (hemoglobin \<8 g/dL) at Screening
13. History of inadequately treated active or latent mycobacterium tuberculosis (TB) infection
14. Clinically significant abnormality on 12-lead electrocardiogram (ECG) at Screening, as determined by the Investigator
15. Positive pregnancy test or lactating at Screening with plans to continue lactating regimen throughout the study
16. History of malignancy within the past 5 years (with the exception of non-metastatic basal or squamous cell carcinoma of the skin with successful treatment), or current active malignancy
17. Liver disease, defined as having elevated aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) levels greater than three times the upper value of the normal range of the study center at Screening
18. Medical condition requiring chronic use of daily prednisone doses \>5 mg (or equivalent)
19. End-stage renal disease caused by primary focal segmental glomerulosclerosis (FSGS), atypical hemolytic uremic syndrome (aHUS), C3 glomerulopathy, or monoclonal gammopathy of kidney significance
a) Note: participants with an unknown cause of ESRD can be included.
20. Participation in an investigational study within 30 days or within 5 half-lives of the investigational agent, whichever is longer, prior to Screening
21. Receiving any antibody or biologic medicinal product (with the exception of erythropoietin products) within 90 days prior to Screening
22. Positive test for SARS-CoV-2 antigen, polymerase chain reaction (PCR), or equivalent testing, at Screening, if performed
23. History or presence of coagulopathy, thrombophilia, unexplained bleeding or clotting disorders, or use of systemic anticoagulants at the time of transplant, with the exception of uremic coagulopathy or prophylactic heparin preparations.
24. History or presence, upon clinical evaluation, of any illness or condition that, in the opinion of the Investigator, would interfere with the ability to provide informed consent or comply with study instructions, or that might confound the interpretation of the study results or put the participant at undue risk.
