Dose Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of REMD-477 in Subjects With Type 2 Diabetes Mellitus

The study will consist of three parts: Part A - Dose Escalation, Part B - Adaptive Dose
Cohort, and Part C - REMD-477 in Combination with Metformin. Part A includes 5 cohorts that
will be enrolled and dosed sequentially at escalating doses. Each cohort will consist of 12
subjects randomized in a 3:1 (active: placebo) fashion. Part B includes a single dose cohort
that will enroll 12 subjects (9 on active treatment and 3 on placebo) with dose level and
frequency determined by a Dose Level Review Meeting (DLRM)Committee. Part C includes 2
cohorts of T2DM patients currently treated with metformin alone, and each cohort will consist
of 15 subjects (10 on active treatment and 3 on placebo).

Inclusion Criteria:

- Men and women between the ages of 18 and 65 years old, inclusive, at the time of
screening;

- Females of non-child bearing potential must be ≥1 year post-menopausal (confirmed by a
serum follicle-stimulating hormone (FSH) levels ≥ 40 IU/mL) or documented as being
surgically sterile, and females of child bearing potential must use two medically
acceptable methods of contraception;

- Male subjects must be willing to use clinically acceptable contraception during
treatment and for 2 months after the last administration of REMD-477;

- Normal or clinically-acceptable physical examination, laboratory test values, and
12-lead ECG (reporting heart rate and PR, QRS, QT, and QTcF) at screening;

- Body mass index between 23 and 40 kg/m2, inclusive, at screening;

- Diagnosed with Type 2 diabetes as defined by the current American Diabetes Association
(ADA) criteria;

- Subjects in Parts A and B only: Treatment-naive, controlled with diet and exercise, or
treated with oral antidiabetic medications and willing to wash-out and discontinue
oral medications during the study;

- Fasting plasma glucose 126 - 270 mg/dL (7-15 mM), inclusive, at screening and at
re-test on Day -1;

- Subjects in Parts A and B only: Screening HbA1c of 7.0-10 % inclusive for subjects not
currently taking any oral antidiabetic medications, or 6.5-9.5% for subjects receiving
acceptable oral antidiabetic medications;

- Subjects in Part C only: Screening HbA1c of 7.5-10 % inclusive for subjects on stable
doses of metformin.

Exclusion Criteria:

- History of drug or alcohol abuse within the last 6 months or a positive illegal drug
urine test result;

- History or family history of pancreatic neuroendocrine tumors or multiple endocrine
neoplasia;

- History or family history of pheochromocytoma;

- Known or suspected susceptibility to infectious disease (eg, taking immunosuppressive
agents or has a documented inherited or acquired immunodeficiency);

- Positive for human immunodeficiency virus (HIV) antibodies, hepatitis B surface
antigen (HbsAg), or hepatitis C antibodies (HepC Ab);

- Participation in an investigational drug or device trial within 30 days of screening
or within 5 times the half-life of the investigational agent in the other clinical
study, if known, whichever period is longer;

- Blood donor, or blood loss>300 mL, within 30 days of Day 1;

- Recent use (6 weeks prior to Screening) of thiazolidinediones, >half-maximal dose
sulfonylurea agent therapy, or any injectable antidiabetic agents (exenatide and other
injectable GLP-1 agonists, insulin and insulin analogs, etc.);

- Other gastrointestinal, cardiac, renal and CNS (i.e. hypoglycemia unawareness)
conditions specific to diabetes that would pose additional risk to subject's safety or
interfere with the study evaluation, procedures or completion;

- Lipid panel profiles of non-HDL-C (total cholesterol minus HDL-C) >219 mg/dL, LDL-C
>189 mg/dL, and/or fasting triglycerides >499 mg/dL;

- Female subject is pregnant or breastfeeding.

Other inclusion and exclusion criteria may apply.