MAD Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of PB-119 to Subjects With T2DM

Dose levels of 25 µg, 50 µg, 100 µg and 200 µg with a dosing regimen of once weekly for 4
consecutive weeks will be evaluated

Inclusion Criteria:

1. Patients in whom T2DM has been diagnosed for at least 3 months prior to screening and
have not been taking any treatment but have made lifestyle modifications (i.e., diet
and exercise) for at least 4 weeks or are taking metformin (with no change in the
treatment including dose over the past 2 months).

2. In good general health as determined by the investigator at screening evaluation

3. Male and/or female subjects between the ages of 18 and 70 years, inclusive;

4. Are capable of giving informed consent and complying with study procedures;

5. Body Mass Index (BMI) of approximately 22 to 40 kg/m2;

6. Fasting C-peptide test result must be >0.4 nmol/L;

7. HbA1c ≥6.5 % and ≤12%;

8. Female subjects must have a negative urine pregnancy test result prior to enrollment.

9. Nonsmoker,

10. Willing and able to adhere to study restrictions and to be confined at the clinical
research center.

Exclusion Criteria:

1. Subjects with a personal or family history of medullary thyroid carcinoma (MTC) or in
subjects with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2);

2. Screening fasting blood glucose ≤100 or ≥270 mg/dL

3. Type 1 diabetes mellitus, or latent autoimmune diabetes in adults; diabetic
neuropathy, retinopathy or nephropathy;

4. Previous treatment with an approved or investigational GLP-1 mimetic;

5. Patients treated with any investigational drugs within 6 weeks of screening;

6. Subjects with pancreatitis;

7. Clinically significant gastrointestinal disorder

8. History or symptoms of clinically significant cardiovascular disease, particularly
coronary artery disease, arrhythmias, atrial tachycardia,

9. Uncontrolled hypertension at screening;

10. History of clinically significant central nervous system disease including: transient
ischemic attack, stroke, seizure disorder, depression,

11. History of liver disease

12. History of clinically significant renal disease

13. Uncontrolled severe dyslipidemia;

14. Positive blood screen for human immunodeficiency virus (HIV), hepatitis B surface
antigen (HBsAg), or hepatitis C antibody;

15. A hospital admission or major surgery within 30 days prior to screening;

16. A history of prescription drug abuse, or illicit drug use within 6 months prior to
screening;

17. A history of alcohol abuse according to medical history within 6 months prior to
screening;

18. A positive screen for alcohol, or drugs of abuse;

19. An unwillingness or inability to comply with food and beverage restrictions during
study participation;

20. Use of prescription or over-the-counter (OTC) medications, and herbal An

21. Unwillingness of male participants to use appropriate contraceptive measures if
engaging in sexual intercourse with a female partner of childbearing potential.
Appropriate measures include use of a condom and spermicide and, for female partners,
use of an intrauterine device (IUD), diaphragm with spermicide, oral contraceptives,
injectable progesterone, progesterone subdermal implants, or a tubal ligation. Sexual
intercourse with pregnant or lactating women is prohibited