A First-in-human Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of HM12460A

The principle objectives of this study are to assess safety and tolerability and to explore
pharmacokinetic(PK) and pharmacodynamic(PD) parameters of a single dose of a novel very-long
acting insulin formulation (HM12460A) in comparison to a single dose of human Neutral
Protamine Hagedorn (NPH) in healthy volunteers (part 1), subjects with type 1 diabetes (part
2) and in subjects with type 2 diabetes (part 3).

The study will incorporate adaptive elements to provide both PK and PD data. The dose of
HM12460A to be administered to the subjects with type 1 diabetes and type 2 diabetes will be
guided by PK data from part 1 of the study; the PD assessment of HM12460A in subjects with
diabetes will also be informed by knowledge of PK gained from the healthy volunteer study.

Inclusion Criteria:

Healthy subjects

- Age ≥18 and ≤70 years

- Non-obese; body mass index between 18.0 and 30.0 kg/m2 inclusive.

- Considered generally healthy upon completion of medical history, physical examination
and biochemical investigations as judged by the Investigator.

- Non-smoker, or light smoker, defined as <15 cigarettes/day and able to abstain from
smoking during confinement period.

- Females must be non-pregnant and non-lactating, and either surgically sterile (e.g.,
tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or
post-menopausal for >12 months. Males must be surgically sterile, abstinent or if
engaged in sexual relations of child-bearing potential, the subject must be using an
acceptable contraceptive method during and for during a period of 60 days after the
last dose of Study Drug.

- Signed and dated informed consent obtained before any trial-related activities.
(Trial-related activities are any procedure that would not have been performed during
normal management of the subject).

Exclusion Criteria:

- Previous participation in this trial or other clinical trials within the last 3
months.

- Clinically significant abnormal hematology or biochemistry screening tests, as judged
by the Investigator. In particular, healthy subjects with liver enzymes above the
upper limit of the normal range and subjects with diabetes who have elevated liver
enzymes (AST or ALT >2 times the upper limit of normal) or impaired renal function
(elevated serum creatinine values above the upper limit of normal) will be excluded.

- History of any illness that, in the opinion of the Investigator, might confound the
results of the trial or pose risk in administering the trial drug to the subject. In
particular, subjects with significant cardiovascular disease, anemia (hemoglobin below
the lower limit of normal) or hemoglobinopathy will not be allowed to enter the trial.

- Clinically significant abnormal ECG at screening, as judged by the Investigator.

- History of alcohol abuse.

- Any positive reaction of drugs of abuse.

- Hepatitis B or C or HIV positive.

- Use of prescription drugs within 3 weeks preceding the first dosing of insulin, except
for medications deemed acceptable per protocol specific list of concomitant
medications.