Phase I, Dose Escalation Study to Evaluate the Safety and Pharmacokinetics of NTM-1632

This is a Phase I, randomized, double-blind, placebo controlled dose escalation trial to
evaluate NTM-1632 in three dose cohorts (A: 0.033 mg/kg, B: 0.165 mg/kg, and C: 0.33 mg/kg).
NTM-1632 is a mixture of three monoclonal antibodies designed to treat botulinum neurotoxin
BoNT/B poisoning in adults. Dose cohorts A, B, and C will be randomized 2:6,
placebo:therapeutic, with a total study population of 24. The study duration is projected to
be approximately 8 months, with subject participation in cohort A being approximately 13
weeks, and subject participation in cohort B and C being approximately 17weeks. The primary
objectives of this study are to assess the safety and tolerability of escalating doses of
NTM-1632 administered intravenously in healthy adults. The secondary objectives are to 1)
assess the pharmacokinetic characteristics of NTM-1632 following a single intravenous
administration and 2) assess the immunogenicity of NTM-1632 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 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. Note: 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,
for up to visit 12 of the study. Note: Acceptable contraception methods are restricted to
effective devices (Intrauterine Contraceptive Devices , NuvaRing®) 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 9. The urine dipstick results on protein, glucose and blood are negative or
trace. Note: 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 as outlined in Section 7.5.1.4 are in the normal reference range. Note:
The following exceptions to laboratory normal reference ranges are allowed: Creatinine,
Blood Urea Nitrogen (BUN), total bilirubin, AST, ALT, chloride, lipase, amylase,
Prothrombin Time (PT), Partial Thromboplastin Time (PTT) below the lower limit of normal
(LLN); CK less than 400mg/ml; Glucose, potassium, CO2, total protein, and alkaline
phosphatase with a toxicity grade of 1 is allowable; Chlorides and 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 exclusions. 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.
Note: 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. Note: 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°C
within 7 days of dosing 7. Pregnant or breastfeeding 8. Donated blood within 56 days of
enrollment 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 Note:
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) 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. Note:
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. Note: 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 23. Oral temperature = 38°C (100.4°F)