Janus Kinase (JAK) Inhibitors to Preserve C-Peptide Production in New Onset Type 1 Diabetes (T1D)

Inclusion Criteria:

1. Provide informed consent or assent as appropriate and, if < 18 years of age have aparent or legal guardian provide informed consent

2. Age 12-35 years (both inclusive) at the time of signing informed consent and assent

3. Diagnosis of T1D within 100 days of the baseline visit (V0).

4. Positive for at least one islet cell autoantibody; Glutamate decarboxylase (GAD)65A,mIAA (if obtained within 10 days of the onset of insulin therapy), IA-2A, ICA, orZnT8A

5. Stimulated C-peptide of ≥0.2 pmol/mL measured during mixed-meal tolerance test (MMTT) conducted at least 21 days from diagnosis of diabetes

6. HbA1c ≤ 10 %

7. Body weight ≥ 35kg at screening

8. Willing to comply with intensive diabetes management and wear a Continuous GlucoseMonitoring Device (CGM)

9. Participants who are Cytomegalovirus (CMV) and/or Epstein-Barr virus (EBV)seronegative at screening must be CMV and/or EBV Polymerase chain reaction (PCR)negative within 30 days of randomization and may not have had signs or symptoms of aCMV and/or EBV-compatible illness lasting longer than 7 days within 30 days of thebaseline visit (V0).

10. Participants who are CMV and/or EBV seropositive at screening must be CMV PCRnegative and/or EBV PCR <2,000 IU/mL and must have no signs or symptoms of acuteinfection at the time of the baseline visit (V0).

11. Be up to date on recommended vaccinations based on age of participants*

12. Participants are required to receive killed influenza vaccination at least 2 weeksprior to the baseline visit (V0) when vaccine for the current or upcoming flu seasonis available. Enrollment must be delayed at least 4 weeks from administration of a killed vaccineother than influenza and COVID-19 and 6 weeks from a live vaccination. Livevaccinations and non-live vaccinations (other than influzena and COVID-19) shouldnot be given while on study drug and be postponed at least 3 months after the lastdose of study drug.

13. If participant is female with reproductive potential, she must have a negativepregnancy test at screening and be willing to avoid pregnancy using ahighly-effective contraceptive method for the duration of the study

14. Males of reproductive age must use a highly-effective contraceptive method duringthe treatment phase and for 3 months following last dose of study drug

• For COVID-19 vaccination, all participants will be strongly encouraged to beup-to-date with COVID-19 vaccine (s) as indicated by country-specificguidelines at least 2 weeks prior to the baseline visit (V0).

Exclusion Criteria:

1. Current or ongoing use of non-insulin pharmaceuticals or medication that affectglycemic control or glucose homeostasis within 7 days prior to screening or anyprohibited concomitant medication listed in section 4.8

2. Untreated hypothyroidism or active Graves' disease

3. Concurrent treatment with other immunosuppressive agents (including biologics orsteroids), other than inhaled or topical glucocorticoids

4. Active acute or chronic infection requiring treatment with oral antibiotics,antivirals, antiparasitics, antiprotozoals, or antifungals within 1 month prior toDay 0 or superficial skin infection within 1 week prior to Day 0

5. Active acute or chronic infection requiring treatment with intravenous therapy (IV)within a minimum 1 month prior to Day 0 a. Specific cases should be reviewed by Infectious Disease Committee prior toenrollment

6. Have active signs or symptoms of acute infection at the time of the baseline visit (V0).

7. Significant trauma or major surgery within 1 month of signing informed consent.

8. Considered in imminent need for surgery or with elective surgery scheduled to occurduring the study

9. History of disseminated herpes zoster or disseminated herpes simplex or a recurrent (more than one episode of) localized, dermatomal herpes zoster

10. Have evidence of prior or current tuberculosis infection as assessed by PurifiedProtein Derivative (PPD), interferon gamma release assay (IGRA) or by history

11. Have evidence of current or past HIV or Hepatitis B infection

12. Have evidence of active Hepatitis C infection

13. Have current, confirmed COVID-19 infection

14. Current or history of Deep vein thrombosis (DVT), Pulmonary embolism (PE), or otherthromboembolic events or history of inherited coagulopathies

15. First degree relative with a history of unprovoked venous thromboembolism (i.e.without known underlying cause such as trauma, surgery, immobilization, prolongedtravel, pregnancy, hormone use, or plaster cast), which suggests that a participantmay be at increased risk of inherited coagulation disorder

16. Any present malignancies or history of malignancy, other than a successfully treatednonmelanoma skin cancer

17. History of any lymphoproliferative disorder such as EBV-related lymphoproliferativedisorder, history of lymphoma, history of leukemia, or signs and symptoms suggestiveof current lymphatic or lymphoid disease

18. Known or suspected polymorphism in the Cytochrome P450 2C19 (CYP2C19 gene, resultingin classification as a poor CYP2C19 metabolizer).

19. Have renal impairment (eGFR< 60 mL/min)

20. Currently on anti-platelet therapies, excluding low dose aspirin

21. One or more screening laboratory values as stated

22. Neutrophils < 1,500 /μL

23. Lymphocytes < 800 /μL

24. Platelets < 150,000 / μL

25. Hemoglobin < 6.2 mmol/L (10.0 g/dL)

26. Potassium > 5.5 mmol/L or <3.0 mmol/L

27. Sodium > 150mmol/L or < 130mmol/L

28. AST or ALT ≥ 2.5 times the upper limit of normal

29. Bilirubin ≥ 1.5 times upper limit of normal unless diagnosed with Gilbert'ssyndrome

30. LDL >160 mg/dL

31. Vaccination with a live virus within the last 6 weeks and killed vaccine within 4weeks (except 2 weeks for flu vaccine and COVID vaccine)

32. Be currently pregnant or lactating or anticipate becoming pregnant during the study

33. Male participants able to father children and female participants of childbearingpotential who are unwilling or unable to use 2 effective methods (at least 1 highlyeffective method) of contraception, including abstinence, as outlined in thisprotocol for the duration of the study and for at least 3 months after the last doseof investigational product

34. Be currently participating in another T1D treatment study

35. Have had previous clinical use of Tzield (Teplizumab) not part of a T1D treatmentstudy.

36. Have hearing loss with progression over the previous 5 years, or sudden hearingloss, or middle or inner ear disease such as otitis media, cholesteatoma, Meniere'sdisease, labyrinthitis, or other auditory condition that is considered acute,fluctuating, or progressive

37. Acute coronary syndrome (e.g., myocardial infarction, unstable angina pectoris) andany history of cerebrovascular disease within 24 weeks before screening; Heartfailure NYHA (New York Heart Association) III, NYHA IV

38. ANY of the following conditions at screening: a. Screening 12-lead electrocardiogram (ECG) that demonstrates: i. Clinicallysignificant abnormalities requiring treatment (eg, acute myocardial infarction,serious tachy- or brady-arrhythmias) or indicating serious underlying heart disease (eg, cardiomyopathy, Wolff-Parkinson- White syndrome); ii. Confirmed QT correctedusing Fridericia's correction factor (QTcF) prolongation (>450 milliseconds). b. Long QT Syndrome, a family history of Long QT Syndrome, or a history of Torsadesde Pointes (TdP).

39. History of chronic alcohol abuse or intravenous drug abuse or other illicit drugabuse within 2 years prior to screening

40. Current or past use of tobacco or nicotine containing products more than theequivalent of 5 cigarettes per day

41. Participant is the investigator or any sub-investigator, research assistant,pharmacist, study coordinator, other staff or relative thereof directly involved inthe conduct of the trial

42. Have any complicating medical issues or abnormal clinical laboratory results thatmay interfere with study conduct, or cause increased risk

43. Any condition that in the investigator's opinion may adversely affect studyparticipation or may compromise the study results