Dose-finding of PB-119 Administered Subcutaneously Once Weekly Versus Placebo in Subjects With Type 2 Diabetes

This is a multicenter, randomized, double-blind, placebo-controlled, parallel dose cohort,
multiple dose study to evaluate the efficacy, safety, and tolerability of different doses of
PB-119 to patients with T2DM not well-controlled by metformin monotherapy. Patients will be
assessed for eligibility over a 2 week screening period prior to a 4-week run-in period and a
12-week double-blind treatment period.A phase 2, multicenter, randomized, double-blind,
placebo-controlled, parallel dose cohort study to evaluate the efficacy and safety of twelve
once weekly subcutaneous doses of PB-119 to patients with type 2 diabetes mellitus (T2DM) not
well-controlled by metformin monotherapy The eligible patients will be randomized to 1 of 3
dose cohorts (A, B, or C). Each patient will subsequently be randomized within the designated
cohort to 1) active drug or placebo at a 3:1 active drug:placebo ratio and 2) exclusion from
or inclusion in the pharmacokinetic (PK) blood sample collection subgroup at a 3:1
excluded:included ratio

Inclusion Criteria:

1. Patients in whom T2DM has been diagnosed according to 2018 American Diabetes
Association T2DM diagnostic criteria, have made lifestyle modifications (ie, diet and
exercise) for at least 3 months prior to Screening, and have been taking metformin for
at least 3 months before Screening with a stable dosage for at least 8 weeks (stable
dosage is defined as metformin dosage ≥1500 mg/day or maximum tolerated dose).

2. Males and/or females between the ages of ≥18 and ≤70 years at Screening

3. HbA1c ≥7.5% and ≤11% at Screening and at Week -1, Visit 3.1;

4. FPG ≥126 and ≤240 mg/dL (≥7.0 and ≤13.3 mmol/L) at Screening and at Week -1, Visit
3.1;

5. Body mass index (BMI) ≥18.5 and ≤40.0 kg/m2 at Screening, with inclusion of patients
with BMIs at the lower end of the range enrolled into the study to enable comparisons
across BMI range;

Exclusion Criteria:

1. Medical history or current diagnosis of:

1. Type 1 diabetes mellitus, diabetes caused by pancreas injury or by other diseases
(like acromegaly or Cushing syndrome);

2. Diabetes acute complication, like ketoacidosis or hyperosmolar coma;

3. Diagnosed proliferative retinopathy;

4. 3 instances of severe hypoglycemia (events during which the patient required the
assistance of another person to actively administer carbohydrate, glucagon, or
other resuscitative actions; episodes may be associated with sufficient
neuroglycopenia to have induced seizure or coma) in the 6 months prior to
Screening;

5. Significant vascular disease;

2. Current/ongoing diagnosis of any type of malignant tumor or evidence of recurrence in
the 6 months prior to Screening (patients who have been stable for ≥6 months or those
who have had basal or squamous cell skin cancers removed and have no evidence of
recurrence will not be excluded). Patients with a medical history of any other type of
cancer in the last 5 years prior to Screening will be excluded;

3. Severe cardiovascular diseases occurring within 6 months prior to Screening (eg,
congestive heart disease, myocardial infarction, acute coronary syndrome, apoplexy,
transient ischemic attack);