An Adaptive Design Study of MTX228

Inclusion Criteria:

• clinical diagnosis of T1DM with onset before the age of 35 requiring continuoustreatment with insulin within 1 year of diagnosis and the presence of positive T1DMautoantibody titer if diagnosed after age 35 (past or present

• HbA1c between 6.0 - 10.0 %.

• Willing to wear study-provided CGM and share CGM data via cloud.

• Diagnosis of T1DM ≥1year at time of screening.

• Fasting or random (post-prandial) C-peptide level ≥ 100 pmol/l (or 0.3 ng/mL) duringscreening or pre-screening. Pre-screening C-peptide levels may be obtained by thestudy team (subject to patient's written consent) up to 56 days before plannedenrolment to reduce the number of screen failures.

• BMI ≤ 35 kg/m2

• eGFR >45 ml/min/1.73m2

• Able and willing to comply with the study protocol for the duration of the study

• Written informed consent must be obtained before any study-related assessment isperformed.

Exclusion Criteria:

• Diagnosis or history indicative of monogenic, Type 2 or post-pancreatectomy diabetes

• History of >1 episode of severe (level 3) hypoglycemia in the prior 6 months

• Significant cardiovascular history defined as:

1. History of myocardial infarction, coronary angioplasty or bypass grafts,valvular disease or repair, unstable angina pectoris, transient ischemicattack, or cerebrovascular accidents within six months prior to entry into thestudy

2. Congestive heart failure defined as New York Heart Association (NYHA) stage IIIand IV

3. Uncontrolled hypertension defined as SBP > 160 mmHg and/or DBP > 100 mmHg

4. Symptomatic postural hypotension

5. Use of systemic corticosteroids (except physiologic replacement doses foradrenal insufficiency) or other medications that would influence insulinsensitivity

6. Use of non-insulin antihyperglycemic agents within prior 30 days.

7. History of significant other major or unstable neurological, metabolic,hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, orurological disorder including previous solid organ or cell transplant thatwould impact patient safety or data interpretation.

8. History of cancer, other than squamous cell or basal cell carcinoma of theskin, that has not been in full remission for at least 5 years before screening (any history of treated cervical intraepithelial neoplasia is allowed)

9. Known recreational substance use or psychiatric illness that, in the opinion ofthe Investigator, may impact the safety of the subject or objectives withscheduled visits

10. A history of alcohol or drug abuse or drug addiction in the previous 12 months

11. A positive pregnancy blood test for women of childbearing age or breast-feedingwomen 12 Are unwilling to use an "effective" method of contraception during thecourse of the study. Sexually active male patients, who could have children,are required to use a condom or abstained from intercourse, and refrain fromsperm donation for the purposes of conception. Females have to be surgicallysterile (via hysterectomy or bilateral tubal ligation) or post-menopausal orusing a medically acceptable barrier method of contraception (i.e. IUD, barriermethods with spermicide or abstinence).