Single-dose Study to Evaluate Safety, Tolerability, and Pharmacodynamics of REMD-477 in Subjects With Type 1 Diabetes Mellitus

The study will be conducted at two sites in the United States, and approximately 20 subjects
with type 1 diabetes will be enrolled. Eligible subjects will be admitted to the clinical
research unit, to carefully monitor blood glucose; and establish the baseline insulin
requirement for maintaining targeted normoglycemia (postabsorptive: 90-120 mg/dL; and
postprandial: <180 mg/dL).

The patients will then be subjected to a hyperglycemic period (250-300 mg/dL) by a stepwise
reduction in insulin infusion. After receiving a single SC dose of REMD-477 or matching
placebo in a double-blinded fashion, all subjects will be assessed for the post-treatment
24-hour insulin requirement needed to maintain targeted normoglycemia (postabsorptive:
90-120 mg/dL; and postprandial: <180 mg/dL); and to be monitored closely for safety,
tolerability and targeted glycemic control, for a 48-hr period. After the in-patient
residency period, subjects will return to the clinic for weekly out-patient safety follow-up
visits for 8 weeks.

Inclusion Criteria:

- Men and women between the ages of 18 and 60 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. Females of child bearing potential must agree to use two methods
of contraception;

- Male subjects must be willing to use clinically acceptable method of contraception
during the entire study;

- Body mass index between 18.5 and 26.9 kg/m2, inclusive, at screening;

- Diagnosed with Type 1 diabetes for greater than 2 years, based on clinical history or
as defined by the current American Diabetes Association (ADA) criteria;

- HbA1c ≥6.0 % but <9.0 % at screening;

- Fasting C-peptide <0.2 ng/mL;

- Current use of insulin pump and willing to use continuous glucose monitoring (CGM)
system (e.g. DexCom) throughout the entire study;

- ALT and/or AST within <1.5x ULN at screening;

- Serum amylase and lipase within normal limits at screening;

- Able to provide written informed consent approved by an Institutional Review Board
(IRB).

Exclusion Criteria:

- History or evidence of clinically-significant disorder or condition that, in the
opinion of the Investigator, would pose a risk to subject safety or interfere with
the study evaluation, procedures, or completion;

- Significant organ system dysfunction (e.g., clinically significant pulmonary or
cardiovascular disease, anemia [Hemoglobin <10.0 g/dL], and renal dysfunction [eGFR
<90 ml/1.73M2/min]);

- Any severe symptomatic hypoglycemic event associated with a seizure or requiring help
from other people or medical facility in the past 6 months;

- Current or recent (within 1 month of screening) use of diabetes medications other
than insulin;

- Use of steroids and/or other prescribed or over-the-counter medications that are
known to affect the outcome measures in this study or known to influence glucose
metabolism;

- Smokes tobacco;

- Known sensitivity to mammalian-derived drug preparations, recombinant protein-based
drugs or to humanized or human antibodies;

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

- History of pancreatitis, pancreatic neuroendocrine tumors or multiple endocrine
neoplasia;

- History of pheochromocytoma, or family history of familial 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 >500 mL within 30 days of Day 1;

- Women who are pregnant or lactating/breastfeeding;

- Regular exercise >120 min/week within 14 days of Day 1;

- Unable or unwilling to follow the study protocol or who are non-compliant with
screening appointments or study visits;

- Family history of multiple endocrine neoplasia.

Other inclusion and exclusion criteria may apply.