STOP-T1D Low-Dose (ATG)

Inclusion Criteria:

1. Willing to provide informed consent or have a parent or legal guardian provideinformed consent when the subject is <18 years of age.

2. Age greater than or equal to 6 and < 35 years

3. At least two or more diabetes-related biochemical autoantibodies (mIAA, GADA, ICA,IA-2A, ZnT8A) present on the same sample. In the absence of other antibodies, ICAand GADA positivity alone will not suffice for eligibility in this trial.

4. Weight greater than the 5th percentile for age and sex.

5. BMI < 95th and > 5th percentile for age for those under age 18 years and < 30 and > 15 for adults (≥ 18)

6. ADA Stage 2 criteria* AND at least one of the following high-risk markers (occurringat the same visit) within 7 weeks (52 days) of randomization, defined below (fordefining a 2-year 50% risk for progression to Stage 3 T1D): a. HbA1c ≥ 5.7 and <6.5% b. Index60 ≥ 1.4 i. Index60 = 0.3695 × (log fastingC-peptide [ng/mL]) + 0.0165 × 60-min glucose (mg/dL) - 0.3644 × 60-min C-peptide (ng/mL) c. DPTRS ≥ 7.4 DPTRS = (1.57 x log BMI) - (0.06 x age) + (0.81 x glucose sumfrom 30 to 120 min/100) - (0.85 x C-peptide sum from 30 to 120 min/10) + (0.48 x logfasting C-peptide)

*Dysglycemia is defined as 2-hr glucose ≥ 140 and <200 mg/dL or fasting glucose ≥ 110 and <126 or 30, 60, or 90 minute glucose ≥ 200 mg/dL from OGTT

7. All subjects must be CMV and EBV PCR negative within 30 days of randomization andmay not have had signs or symptoms of a CMV or EBV-compatible illness lasting longerthan 7 days within 30 days of randomization

8. Seated blood pressure less than 130/80 mmHg for participants ≥ 18 years. Forparticipants < 18 years seated blood pressure less than 95th percentile for age, sexand height.

9. Be at least 4 weeks from last live immunization

10. Participants are required to receive non-live influenza vaccination at least 2 weeksprior to randomization when vaccine for the current or upcoming flu season isavailable.

11. Participants must also have a negative COVID-19 test within 7 days of the first dayof treatment if otherwise eligible

12. Willingness to comply with study directed social distancing and protection fromSARS-Cov-2 infection.

13. Be willing to forgo vaccines (other than killed influenza) during the 3 months afterstudy drug treatment period (Days 0 and 1)

14. Be up to date on all recommended vaccinations based on age of subject*

15. With the exception of stage 2 T1D, subjects must be healthy, as defined by absenceof any other untreated diagnoses that the protocol committee deems to be a potentialconfounder.

16. If a female participant with reproductive potential, willing to avoid pregnancy (abstinence or adequate contraceptive method) through the completion of the studyinfusions and up to 3 months after study drug administration and undergo pregnancytesting prior to each study visit.

17. Must be residing or have accommodations within 1 hour of the infusion site duringthe two days of study drug infusions and must be within 1 hour of a medical carefacility for 1 day after completion of infusion 2.

18. Participants must live in a location with rapid access to emergency medicalservices.

• Adult participants must be fully immunized. Pediatric participants who have notcompleted their primary vaccination schedule must receive all vaccinationsallowable per the national/country-specific immunization guidelines for theircurrent age prior to study drug delivery. Any remaining vaccinations should begiven and continue per the schedule at least 3 months after study drug isadministered. For COVID-19 vaccination, all participants will be stronglyencouraged to be up-to-date with COVID-19 vaccine(s) as indicated bycountry-specific guidelines at least 2 weeks prior to randomization.

Exclusion Criteria:

1. Immunodeficiency or clinically significant chronic lymphopenia: (Leukopenia (< 3,000leukocytes /μL), neutropenia (<1,500 neutrophils/μL), lymphopenia (<800lymphocytes/μL), thrombocytopenia (<100,000 platelets/μL).

2. Hemoglobin less than 13.5 g/dL for adult men and less than 12 g/dL for adult femalesand less than 11 g/dL for participants under age 18

3. Active signs or symptoms of acute infection at the time of randomization includingSARS-Cov-2.

4. Uncontrolled autoimmune thyroid disease and/or celiac disease (participants must bewell controlled for the previous 6 months).

5. Evidence of prior or current tuberculosis infection as assessed interferon gammarelease assay (QuantiFERON).

6. Currently pregnant or lactating or anticipate getting pregnant within the studyperiod.

7. Require use of other immunosuppressive agents including chronic use of systemicsteroids.

8. Evidence of current or past HIV or Hepatitis B or current Hepatitis C infection.

9. Any complicating medical issues or abnormal clinical laboratory results that mayinterfere with study conduct, or cause increased risk to include pre-existingcardiac disease, COPD, sickle cell disease, neurological disease, or blood countabnormalities.

10. A history of malignancies other than of skin.

11. Evidence of liver dysfunction with AST or ALT outside of the reference range.

12. Evidence of renal dysfunction with creatinine outside of the reference range.

13. Increased bilirubin (total and direct) outside of the normal limit (Participantswith documentation of Gilbert's Disease permitted).

14. Vaccination with a live virus within the last 4 weeks.

15. Current or ongoing use of non-insulin pharmaceuticals that affect glycemic controlwithin 7 days of screening

16. Prior treatment with Teplizumab (either in a previous clinical trial or clinically).

17. Has participated in a clinical trial for diabetes prevention previously and receivedactive study agent within 3 months of randomization.

18. Known allergy to ATG or any product excipient

19. Prior treatment with ATG or known allergy to rabbit-derived products or to anyproduct excipient

20. Prior adverse reactions to heparin.

21. Any condition that in the investigator's opinion may adversely affect studyparticipation will be reviewed by the Study Chair to ensure consistency andadjudicate whether or not the subject may compromise the study results

22. Any screening/baseline laboratory result not otherwise stated out of normalreference range and/or medical history that may increase the risk of the subject'sparticipation in this trial.

23. Previously diagnosed with Stage 3 TID according to ADA criteria (see Appendix 3 forCriteria for diagnosis of diabetes)