A Study to Evaluate the Safety and Pharmacokinetics of NTM-1633 vs Placebo Administered Intravenously in Healthy Adults

This is a Phase I, single-center, double-blind, placebo-controlled dose escalation trial of
three dose cohorts (A: 0.033 mg/kg, B: 0.165 mg/kg, and C: 0.33 mg/kg). The purpose of this
study is to evaluate the safety and tolerability of NTM-1633 in healthy adults. This is a
first-in-human study consisting of three cohorts of eight subjects each. Dosing for each
cohort is as follows: Two sentinel subjects will be administered a single 1-hour infusion
(one NTM-1633, one placebo). No more than two subjects per day thereafter (at least 24 hrs
will elapse between the dosing of each two subjects) will be dosed in the same manner until
all subjects are dosed. Dose escalation will not occur until safety data through Day 8 is
reviewed by the Safety Review Committee (SRC). Objective dose-escalation criteria and safety
evaluations will be utilized. The study duration will be for approximately 8 months. Subjects
in Cohort A will participate for approximately 17 weeks and Subjects in Cohorts B and C will
participate approximately 21 weeks. Primary Objective: To assess the safety and tolerability
of escalating doses of NTM-1633 administered intravenously in healthy adults. Secondary
Objectives: 1) To assess the pharmacokinetic characteristics of NTM-1633 following a single
intravenous administration; 2) To assess the immunogenicity of NTM-1633 following a single
intravenous administration.

Inclusion Criteria:

1. Informed consent understood and signed.

2. Healthy male or healthy, non-pregnant, non-lactating female.

3. Willingness to comply and be available for all protocol procedures including inpatient
confinement for 36 - 48 hours.

4. Age between 18 and 45 years, inclusive on the day of infusion.

5. Body Mass Index (BMI) of > / =18.5 and < 35 kg/m^2.

6. If the subject is female and of childbearing potential, she has a negative serum
pregnancy test at screening and negative urine test within 24 hours prior to infusion.

- A woman is considered of childbearing potential unless post-menopausal (> / = 1
year without menses) or surgically sterilized via bilateral oophorectomy, or
hysterectomy or bilateral tubal ligation or successful Essure placement with
documented confirmation test at least 3 months after the procedure.

7. If the subject is female and of childbearing potential, she agrees to practice
abstinence from sexual intercourse with men or use acceptable contraception up to
visit 12 of the study.

- Acceptable contraception methods are restricted to effective devices
(Intrauterine Contraceptive Devices, NuvaRing(R)) or licensed hormonal products
with use of method for a minimum of 28 days prior to dosing, condoms or diaphragm
with spermicidal agents, monogamous relationship with a vasectomized partner

8. The hemoglobin, platelet count, white blood cell count and absolute neutrophil count
are within normal limits at the screening visit.

9. The urine dipstick results on protein, glucose and blood are negative or trace.

- Menstruating females failing inclusion criteria due to a positive blood on urine
dipstick may be retested following cessation of menses.

10. Chemistry screening laboratory tests are in the normal reference range.

- The following exceptions to laboratory normal reference ranges are allowed:
Creatinine, Blood Urea Nitrogen (BUN), total bilirubin, AST, ALT, lipase,
amylase, Prothrombin Time (PT), Partial Thromboplastin Time (PTT) below the lower
limit of normal (LLN); CK less than 400mg/ml; Glucose, potassium, total protein,
and alkaline phosphatase with a toxicity grade of 1 is allowable; albumin above
the upper limit of normal (ULN).

- Laboratory values that are outside the range of eligibility but are thought
to be due to an acute condition or due to laboratory error may be repeated
once.

- Abnormalities in mean corpuscular volume (MCV), mean corpuscular hemoglobin
(MCH), mean corpuscular hemoglobin concentration (MCHC), red cell
distribution width (RDW), mean platelet volume (MPV), and nucleated red
blood cell count (NRBC CT), which are included in a complete blood count
with differential, will not be exclusionary.

11. Has adequate venous access for the infusion.

12. The urine drug screen is negative.

13. Breathalyzer test is negative.

14. Available for follow-up for the duration of the study.

15. Agrees not to participate in vigorous activity 72 hours prior to dosing through day 15
post dosing.

Exclusion Criteria:

1. History of a chronic medical condition that would either interfere with the accurate
assessment of the objectives of the study or increase the risk profile of the subject.

- Chronic medical conditions include diabetes; Asthma requiring use of medication
in the year before screening; Autoimmune disorder such as lupus, Wegener's,
rheumatoid arthritis, thyroid disease; Coronary artery disease; Chronic
hypertension; History of malignancy except low-grade (squamous and basal cell)
skin cancer thought to be cured; chronic renal, hepatic, pulmonary, or endocrine
disease (except previous asthma which has required no treatment for the past
year)

2. History of severe allergic reaction of any type to medications, bee stings, food, or
environmental factors or hypersensitivity or reaction to immunoglobulins.

- Note: Severe allergic reaction is defined as any of the following: anaphylaxis,
urticaria, or angioedema

3. A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a
QTc interval > 450 milliseconds)

4. Clinically significant abnormal electrocardiogram at screening.

- Clinically significant abnormal ECG results include: complete left or right
bundle branch block; other ventricular conduction block; 2nd degree or 3rd degree
atrioventricular (AV) block; sustained ventricular arrhythmia; sustained atrial
arrhythmia; two Premature Ventricular Contractions in a row; pattern of ST
elevation felt consistent with cardiac ischemia; or any condition deemed
clinically significant by a study investigator

5. Positive serology results for HIV, HBsAg, or HCV antibodies

6. Febrile illness with temperature > 37.6 degrees Celsius within 7 days of dosing

7. Pregnant or breastfeeding

8. Donated blood within 56 days of enrollment (day -1)

9. Known allergic reactions to any of the study product components present in the
formulation or in the processing, as listed in the Investigator Brochure

10. Treatment with another investigational drug within 28 days of dosing

11. Treatment with a monoclonal antibody at any time in the past

12. Receipt of antibody (e.g. TIG, VZIG, IVIG, IM gamma globulin) or blood transfusion
within 6 months or within 5 half-lives of the specific product given

13. Active drug or alcohol use or dependence that, in the opinion of the investigator,
would interfere with adherence to study requirements

14. Use of H1 antihistamines or beta-blockers within 5 days of dosing

15. Use of any prohibited medication within 28 days prior to study entry or planned use
during the study period

- Prohibited medications include immunosuppressives (except Nonsteroidal
Anti-Inflammatory Drugs [NSAIDS]); immune modulators; oral corticosteroids
(topical/intranasal steroids are acceptable); anti-neoplastic agents; any vaccine
(licensed or investigational). If study activities overlap with the influenza
season, subjects will be instructed to delay influenza vaccination until after
Day 57 (Visit 11)

16. Previous exposure to botulinum toxin, receipt of antibodies against botulinum toxin,
or previous treatment with equine antitoxin

17. Any previous injection or planned injection within 4 months after enrollment of
botulinum toxin for cosmetic reasons, spastic dysphonia, torticollis, or any other
reason

18. Any specific condition that in the judgment of the investigator precludes
participation because it could affect subject safety

19. Plans to enroll or is already enrolled in another clinical trial that could interfere
with safety assessment of the investigational product at any time during the study
period

- Includes trials that have a study intervention such as a drug, biologic, or
device

20. Is a study site employee or staff who are paid entirely or partially by the OCRR
contract for the DMID-funded trial

- Site employees or staff include the PIs and sub-investigators or staff who are
supervised by the PI or Sub-Investigators

21. Systolic blood pressure >140 mm Hg or diastolic blood pressure > 90 mm Hg

22. Resting heart rate < 50 or > 100 beats per minute at Screening

23. Oral temperature > / = 38 degrees Celsius (100.4 degrees Fahrenheit)