SAFety and Efficacy of Human Anti-thymocyte ImmunoGlobUlin SAB-142 ARresting Progression of Type 1 Diabetes

Inclusion Criteria:

1. Participant and/or appropriate legal guardian must have given written informedconsent and/or assent according to local, regional and/or country specific guidancebefore any study-related activities are carried out and must be able to understandthe full nature and purpose of the trial, including possible risks and adverseeffects.

2. Males and females 15-40 years old at the time of randomisation in Part A. Males andfemales 5-40 years old*, inclusive, at the time of randomisation in Part B.

3. Weight ≥16.0 kg at time of randomisation.

4. Participant has received a diagnosis of T1D according to American DiabetesAssociation criteria within 100 days of randomization. For participants who wereinitially misdiagnosed with Type 2 diabetes, time from misdiagnosis with Type 2diabetes to randomization is 100 days. Note: The date of diagnosis is defined as thedate of the first insulin dose or any other glucose lowering medication. Anextension of no more than 14 days is permitted if a participant has planned and/oris required to receive a vaccination within 30 days prior to randomisation or iscompleting the 10 day CGM period.

5. Participant has random C-peptide levels of ≥0.2 nmol/L, measured during Screening.One random C-peptide retest during screening period is allowed.

6. Participant completed all scheduled samples for C-peptide collected during the MMTTtest during Screening.

7. Participant has a positive result on testing for at least one of the followingT1D-related autoantibodies during screening:

• Glutamic acid decarboxylase 65 (GAD65)

• Islet antigen 2 (IA-2)

• Zinc transporter 8 (ZnT8)

• Insulin autoantibodies (if testing within the first 14 days of insulintreatment)

8. Female participants: a. Must be of nonchildbearing potential, i.e., pre-pubertal*, surgically sterilised (hysterectomy, bilateral salpingectomy, bilateral oophorectomy) at least 6 weeksbefore the screening, or postmenopausal (where postmenopausal is defined as nomenses for 12 months without an alternative medical cause and a follicle stimulatinghormone (FSH) level consistent with postmenopausal status, per local laboratoryguidelines), or b. If of childbearing potential, must: i. Have a negative result ona serum (beta human chorionic gonadotropin [β-HCG]) at screening and a negativeurine β-HCG pregnancy test prior to study drug administration on Day 1 of bothtreatment periods. ii. Agree not to become pregnant or donate ova from signing the consent form untilthe end of study visit. iii. If not exclusively in a same-sex relationship or abstinent as a committedlifestyle, must agree to use adequate contraception (which is defined as use of acondom by the male partner combined with use of a highly effective method ofcontraception from signing the consent and for the duration of the study.

• Note: Female participants will be considered to be pre-pubertal (and ofnonchildbearing potential) if they have not yet started menstruation. This shouldalso be verified by the parent(s)/guardian(s). If a female participant reachesmenarche during the study, then she is to be considered as a woman of childbearingpotential from that time forwards, and contraceptive requirements will apply.

9. Male participants, if not biologically or surgically sterilised, must:

10. Agree not to donate sperm from signing the consent form until EOS.

11. If engaging in sexual intercourse with a female partner who could becomepregnant, agree to use adequate contraception (defined as use of a condomcombined with use of a highly effective method of contraception from signingthe consent form until EOS.

12. If engaging in sexual intercourse with a female partner who is not ofchildbearing potential or a same-sex partner, agree to use a condom fromsigning the consent form until EOS.

13. Prior to receiving study drug, participant must agree to receive locally, regionallyand/or country-specific required age-appropriate immunisations. Participants areadvised but not required to comply with the guidelines for immunosuppressedindividuals and those with chronic disease (diabetes mellitus) according to currentlocal, regional and/or country- specific guidelines. Note: Vaccines are permittedwithin the timeframes specified in exclusion criterion #17.

14. Participant agrees not to receive other forms of experimental treatment from thetime of signing informed consent and for the duration of the study, particularlyagents that may be immune modulatory in nature and/or stimulate pancreatic β cellregeneration or insulin secretion.

15. Participant has suitable venous access for blood sampling.

16. Participant is willing and able to comply with all study assessments and adhere tothe protocol schedule and restrictions.

Exclusion Criteria:

1. Participant has known allergy, hypersensitivity or moderate to severe allergicreaction including anaphylaxis to natural or recombinant antibodies, biologictreatments, passive vaccines, pork, or any other component of the study drugformulation (including biologic medications).

2. Participant has a known allergy or hypersensitivity to any of the protocol-requiredconcomitant medications.

3. Participant has been an active participant in a therapeutic drug, invasive medicaldevice, or vaccine clinical trial within 12 weeks before Screening Visit (SV)2.

4. Participant has received teplizumab or any investigational immunomodulatory anti-CD3treatment within any timeframe prior to screening.

5. Participant has a significant uncontrolled renal, cardiac, vascular, pulmonary,gastrointestinal, neurologic, haematologic, rheumatologic, oncologic, psychiatric,or immune deficiency that may interfere with the participant's safely participatingin the study or with interpretation of the safety and/or efficacy profile ofinvestigational medicinal product (IMP). For any disorders, a participant with astable, well-controlled condition that is not felt to interfere with studyparticipation may be enrolled.

6. Participant has any autoimmune disease other than T1D (e.g., latent autoimmunediabetes in adults, rheumatoid arthritis, polyarticular juvenile idiopathicarthritis, psoriatic arthritis, ankylosing spondylitis, multiple sclerosis, systemiclupus erythaematous) that is currently managed with systemic immunotherapy, with theexception of clinically stable thyroid or celiac disease.

7. Participant is prone to infections, or has chronic, recurrent or opportunisticinfectious disease, including but not limited to renal, respiratory or skininfections, Pneumocystis carinii, aspergillosis, latent or active granulomatousinfection, histoplasmosis, or coccidioidomycosis.

8. Participant has a history of or serologic evidence at screening of current or pastinfection with human immunodeficiency virus (HIV)-1 or 2, hepatitis B virus (HBV),or hepatitis C virus (HCV) antibodies.

9. Evidence of active or latent tuberculosis (TB) as documented by medical history andexamination, chest X-rays (posterior anterior and lateral), and/or TB testing. Note:Blood testing (e.g., QuantiFERON® TB Gold test) is strongly preferred; if notavailable, any local approved TB test is allowed.

10. Serious systemic viral, bacterial, or fungal infection (e.g., pneumonia,pyelonephritis), infection requiring hospitalization or IV anti-infective treatmentsor significant acute or chronic viral (including history of recurrent or activeherpes zoster, acute or active cytomegalovirus [CMV], Epstein-Barr Virus [EBV] asdetermined at screening), bacterial, or fungal infection (e.g., osteomyelitis) 30days before and during screening. Note: Participants with confirmed active EBV orCMV infection based on polymerase chain reaction (PCR) test can be retested;asymptomatic participants with the most recent PCR-negative test are eligible forparticipation. Participants with an active mild infection at Screening may beenrolled once the symptoms have resolved and all I/E are met. Participants who havean active infection and/or fever ≥38.0°C (100.4°F) within the 48 hours prior to doseadministration should not be dosed.

11. Participant has a diagnosis of significant liver disease or at screening ALT and/orAST >2× or total bilirubin of >1.5× of the age- and sex-specific upper limit ofnormal (ULN) according to the central laboratory and confirmed by repeated tests.Liver function tests can be repeated during screening and if normalised, participantmaybe eligible for randomization. Note: Participants with Gilbert's syndrome areallowed to enrol if only total and/or indirect bilirubin are elevated above ULNwhile ALT, AST, and alkaline phosphatase (ALP) are within the normal laboratoryranges.

12. An individual has any of the following haematologic parameters, confirmed by repeattests, during Screening:

• Lymphocyte count: <1000/μL

• Neutrophil count: <1500/μL

• Platelet count: <100 000 platelets/μL

• Haemoglobin: <10 g/dL Note: Specific haematologic, oncologic or other systemicconditions that might otherwise result in exclusion and/or is heretoforeunrecognised should be considered in individuals who have one or more bloodcell counts below or above the normal ranges.

13. Current or prior (within 5× half-lives before SV2) treatment that is known to causea significant, ongoing change in the course of T1D or immunologic status, includingsystemic glucocorticoids, verapamil, baricitinib, and others. Note: Inhaled andtopical corticosteroids are allowed. Short courses, i.e., approximately 2 weeks orless, of systemic corticosteroids for transient conditions are allowed.

14. Current or prior (within 5× half-lives before SV2) use of drugs other than insulinto treat hyperglycaemia (e.g., metformin, sulfonylureas, glinides,thiazolidinediones, exenatide, liraglutide, glucagon-like peptide 1 agonists [glucagon-like peptide-1], dipeptidyl peptidase-4 [DPP-IV] inhibitors, or amylin).

15. Current or prior (within 5× half-lives before SV2) use of any medication known tosignificantly influence glucose tolerance (e.g., atypical antipsychotics,diphenylhydantoin, niacin).

16. Current or planned highly restrictive dietary regimen(s) that would interfere withparticipant well-being or impact to investigational drug.

17. Recent or planned vaccinations as follows:

• Live vaccines (e.g., varicella, measles, mumps, rubella, cold-attenuatedintranasal influenza vaccine, and smallpox): Within the 30 days before dosingor within 60 days following dosing; or planned/required within 30 days prior toor 60 days following Day 1 of TP2.

• Recombinant, inactivated or otherwise "non-live" vaccines: Within the 30 daysbefore dosing or within 60 days following dosing; or planned/required within 30days prior to or 60 days following Day 1 of TP2.

18. Female is lactating and/or plans to lactate with the intent to provide her ownbreast milk to a baby at any point during the study.

19. An individual who has a history of alcohol, drug, or chemical abuse within 12 monthsprior to study screening (positive tetrahydrocannabinol is allowed) Note: Abuse isdefined according to local, regional and/or country specific guidance. Participantswho are tested positive for illicit substances but have a prescription medication tomanage their concomitant conditions such as attention-deficit/hyperactivity disorder (ADHD) or others are allowed to participate in the study.

20. An individual who has a medical, psychological or social condition that, in theopinion of the Investigator, would interfere with safe and proper completion of thetrial.

21. An individual who is an employee of the Investigator or study site, with directinvolvement in the proposed study or other studies under the direction of thatInvestigator or study site.