A Study to Assess Safety, Tolerability, and Pharmacokinetics of MEDI0382 in Non-diabetic Obese Subjects

This is a Phase 1, randomized, blinded, placebo-controlled study in up to approximately 51
non-diabetic obese subjects with a body mass index (BMI) ≥ 35 kg/m2. Subjects will be
blinded, but investigators/site staff and sponsor will be unblinded for Cohort 1. In Cohort 2
and 3 subjects, investigators, and contract research organization personnel are blinded to
investigational product and sponsor is unblinded. The subjects will participate in the study
for up to approximately 27 weeks, including a screening period (including a run-in),
treatment period, and safety follow-up.

Subjects will be randomized 4:1 to MEDI0382 (n=12) or placebo (n=3) for Cohort 1 and
randomized 2:1 to MEDI0382 (n=12) or placebo (n=6) for Cohort 2 and 3. In Cohort 1 those
subjects randomized to MEDI0382 or placebo will be dosed daily with a weekly titration
schedule until the highest clinically tolerated dose (CTD) is established. In Cohort 2
subjects randomized to MEDI0382 or placebo will be dosed daily with a 2 week titration
schedule up to the highest CTD is established In Cohort 1. In Cohort 3 subjects randomized to
MEDI0382 or placebo will be dosed daily with a 4 week titration schedule up to the highest
CTD established in Cohort 1. Once the highest CTD is identified, subjects will continue on
the highest CTD for an additional 2 weeks of treatment for Cohort 1 and 3 and additional 4
weeks treatment for Cohort 2. All subjects will return 28 days post last dose for a safety
follow-up visit.

Key Inclusion Criteria:

1. Provision of written informed consent

2. Male and female subjects age 18 through 65 years

3. BMI ≥ 35 kg/m2

4. Hemoglobin A1c level of < 6.5%

5. Female subjects must have a negative pregnancy test and must not be lactating.

6. Females of childbearing potential using appropriate birth control to avoid pregnancy
during the study.

7. Stable body weight

8. Willing and able to adhere to the visit/protocol schedule, including following
lifestyle advice with respect to diet and exercise for the duration of the study

9. Willing and able to self-administer daily SC injections following an initial
self-injection training

Key Exclusion Criteria:

1. Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks
prior to Study Day 1 dosing.

2. Any condition that, in the opinion of the investigator, would interfere with the
evaluation of the investigational product or interpretation of subject safety or study
results. Specific examples are:

3. Active participation in any other investigation clinical study.

4. Any prescription or non-prescription drugs for weight loss including herbal or other
dietary supplements used within the past 3 months prior to screening.

5. Previous GLP-1 use within 3 months prior to screening.

6. Any positive results for serum hepatitis B surface antigen, hepatitis C virus
antibody,and/or human immunodeficiency virus (HIV) antibody at screening.

7. Laboratory results that fall within the following ranges (laboratory tests may be
repeated once for confirmation of out of range values at screening):

8. Significant hepatic or renal impairment

9. Poorly controlled hypertension

10. Known or suspected history of drug or alcohol abuse within the past year or positive
current test

11. Previous surgical procedures for weight loss