Intravenous Dose-Escalation Study With ETI-204 in Adult Volunteers

Study Duration: Maximum 70 days for each subject (from enrollment to end of follow-up
period), unless the Day 70 HAHA (human anti-humanized antibodies) is positive, in which case
subjects will be followed until HAHA test results are negative. This does not represent the
total study duration, which is determined by the screening period and enrollment rate.

Description of Agent: ETI-204 is a monoclonal antibody (MAb) to protective antigen (PA) from
Bacillus anthracis.

Schedule of Evaluations: Blood for pharmacokinetics (antibody concentration): Predose and at
the following times after the start of infusion: 60 minutes (i.e., at the completion of the
infusion), 3, 6, 12, 24 and 48 hours and on Days 7, 14, 21, 42, 56 and 70.

Blood chemistry, hematology, and urinalysis (referred to as safety laboratory assessments in
the schedule of events), and urine drug screen (including ethanol and cotinine at all
visits): Screening, Day 0, immediately pre-dose and on the following days after the start of
infusion: 7, 14, 21, and 42. Urine pregnancy tests for all females will be performed at
screening, baseline, immediately pre-dose and at 42 days. Tests of coagulation and viral
serology tests will be done at screening only.

ECG: A 12-lead ECG will be done at screening. In subjects with acceptable ECG parameters,
continuous 24-h Holter monitoring. will be then performed. After enrollment, a standard
12-lead ECG recording will be performed on study Day 1 (predose, 1.5h, 2h, 4h, 8h and 12h ±20
min) and continuous ECG telemetry monitoring beginning approximately 2 hours prior to the
start of infusion and continuing at least 14 hours after the start of infusion. ECG is also
recorded at the following study Days: 2, 7, 14, 21, and 42.

Measurement of product specific human anti-humanized antibodies (HAHA): Pre-dose and 42 days
after dosing. HAHA positive subjects on Day 42 will be followed bi-weekly until study Day 70
and then monthly until HAHA test results are negative.

Vital signs (BP, P, T, RR): Screening, Day 0, before and at the following times after the
start of the infusion on study day 1: 15, 30, 45, 60, 90±3 minutes; 2h,4h,8h, 12h and 24h±10
minutes (Day 2); Days 7, 14, 21 and 42.

Screening for Local and Systemic Adverse Events: The infusion site and proximal areas will be
inspected for evidence of erythema, edema, visible or palpable cord, etc. on study days 1, 2,
7, 14, 21 and 42.

Participating Sites: The Ohio State University Clinical Pharmacology Unit Columbus, Ohio

Inclusion Criteria:

1. Healthy male or female subjects between the ages of 18-50 inclusive at the time of
enrollment. In each of the drug cohorts (subgroups), at least three of the subjects
must be female.

2. The following screening laboratory parameters must be within 5% of the normal range:
CBC (excluding WBC) and coagulation tests (aPTT, PT and INR). Absolute counts of WBC
must be within 10% of the normal range. BUN, creatinine, and total and direct
bilirubin may be up to 10% above the upper limits of normal. AST, ALT and alkaline
phosphatase must be within normal limits. Urinalysis must be within generally accepted
normal limits.

3. The values for the following tests at screening are to be:

G-6-P dehydrogenase - normal HBsAg - negative HBV - negative (except immunized
subjects may have positive anti-HBs) Anti-HCV - negative Anti-HIV (HIV antibody test)
- negative Urine drug screen (including cotinine) - negative

4. Female subjects must agree to practice heterosexual abstinence or to use a licensed,
effective form of birth control (e.g., oral contraceptives, diaphragm or condom in
combination with contraceptive jelly, cream or foam, intrauterine contraceptive
device, Depo-Provera®, skin patch, vaginal ring, or cervical cap) for at least 30 days
prior to enrollment and for the duration of the study, including the follow-up period.
Females using hormonal contraceptives must agree to use at least one other method for
at least 30 days prior to enrollment and for the duration of the study, including the
follow-up period.

5. Female subjects must have a negative pregnancy test.

6. No history of hospitalization for illness within the six months prior to study
enrollment.

7. Nonsmoker or ex-smoker. If a subject is an ex-smoker, he/she must not have used
nicotine for at least 6 months prior to enrollment. This will be confirmed by a
negative urine test for cotinine. Exceptions may be made for sporadic users with
negative urine cotinine tests; this will be determined on a case-by-case basis.

8. Able to spend the two days specified in the study schedule confined in a facility
under study rules.

9. Able to read, understand and sign the informed consent form

Exclusion Criteria:

1. Routine consumption of any medication (prescription or OTC), vitamin, mineral, or
dietary supplement, for one week before and during the study. The sole exceptions are
hormonal contraceptive agents, as detailed above. The withdrawal time for any
prescription medication should be no less than 1 week prior to the beginning of the
study.

2. Blood pressure greater than 139 mm Hg systolic and 89 mm Hg diastolic. Repeat
measurements are allowed.

3. Contraindication to the use of any monoclonal antibody: history of allergic reactions
to any biologic or formulation component

4. Medical condition that in the Investigator's opinion could adversely impact the
subject's participation, safety or conduct of the study.

5. Subject has taken an investigational medication in the previous three months.

6. The subject has a history of drug or alcohol abuse within the past two years.

7. The subject is female and plans to become pregnant during the whole study period or 6
months.

8. Calculated Body Mass Index (BMI) greater than 35.0 or less than 18.5.

9. The subject has been previously vaccinated with anthrax or has participated in
clinical research involving anthrax.

10. Any ECG abnormality except for the following:

- Sinus bradycardia, no lower than 46 beats per minute in younger, athletic
subjects

- Sinus tachycardia if the heart rate is within normal limits when vital signs are
measured

- Respiratory arrhythmia

- Mild first degree A-V block (P-R interval < 0.23 sec)

- Incomplete right bundle branch block

- Left anterior hemiblock

- Ectopic atrial focus

- Premature atrial contractions

- Unifocal premature ventricular contractions

- Mild right or left axis deviation

- Indeterminate axis

- J-point elevation