NasoShield Study of Safety and Immunogenicity

This study is a Phase 1, randomized, double-blind, placebo-controlled, dose-escalation
clinical trial to evaluate the safety and immunogenicity of NasoShield in healthy adults 18
to 49 years of age. Subjects will be screened within 28 days of randomization (Day 1). The
study is comprised of 2 parts:

- Part A: Approximately 120 subjects who meet all inclusion and no exclusion criteria and
provide written informed consent will be enrolled into 4 sequential cohorts of 30
subjects each defined by the NasoShield dose (1×108, 1×109, 1×1010, and 1×1011 vp).
Within each cohort (and the sentinel group in the first dose cohort), subjects will be
randomized in a 4:1:1 ratio to receive 1 intranasal dose of NasoShield (Day 1), 1
intranasal dose of placebo (Day 1), or 3 subcutaneous 0.5 mL doses of BioThrax 14 days
apart (Days 1, 15, and 29). NasoShield and placebo will be administered in a
double-blind fashion, and BioThrax will be administered in an open-label fashion.

- Part B: Approximately 25 subjects who meet all inclusion and no exclusion criteria and
provide written informed consent will be randomized in a 4:1 fashion to receive 2
intranasal doses of NasoShield at the highest well tolerated dose from Part A or placebo
21 days apart (Days 1 and 22). NasoShield and placebo will be administered in a
double-blind fashion.

Subjects will return to the investigational site for multiple visits through Day 361. At each
visit, the subject will be asked about the interim medical history and use of any
medications, and safety and immunogenicity assessments will be performed.

Inclusion Criteria:

1. Men and women 18 to 49 years of age, inclusive

2. Good general health status as determined by the Investigator

3. Adequate venous access for repeated phlebotomies

4. Screening laboratory results within institutional normal range or Grade 1 abnormality
if the Investigator documents clinical insignificance. Creatine kinase or bilirubin
may be Grade 2 if associated with normal alanine aminotransferase (ALT) and aspartate
aminotransferase (AST) and the Investigator considers the result not to be clinically
significant due to vigorous exercise or Gilbert's syndrome

5. Negative drug and alcohol screen at Screening and predose on Day 1

6. For women who have not been surgically sterilized and do not have laboratory
confirmation of postmenopausal status, negative pregnancy test

7. Willingness to practice a highly effective method of contraception: abstinence, sex
only with persons of the same sex, monogamous relationship with a postmenopausal
partner, monogamous relationship with vasectomized partner, vasectomy, surgical
sterilization (hysterectomy, bilateral tubal ligation, salpingectomy, or
oophorectomy), licensed hormonal methods, intrauterine device (IUD), or consistent use
of a barrier method (eg, condom, diaphragm) with spermicide for 28 days after the last
IP dose

8. Willingness to participate and comply with all aspects of the study through the entire
study period, including nasopharyngeal swabs and blood and urine samples

9. Provision of written informed consent

Exclusion Criteria

1. Pregnant, possibly pregnant, or lactating women

2. Household contacts of pregnant women, children < 5 years of age, or immunocompromised
individuals for the period up through 2 weeks postvaccination

3. Persons who care for pregnant women, children < 5 years of age, or immunocompromised
individuals for the period up through 2 weeks postvaccination

4. Body mass index > 35.0 kg/m2

5. Positive result for HIV, hepatitis B virus, or hepatitis C virus at Screening

6. Asthma or other chronic lung disease that is greater than mild in severity.
Specifically excluded are participants with any of the following events in the past
year:

- Daily symptoms

- Daily use of short acting beta 2 agonists

- Use of inhaled steroids or theophylline

- Use of pulse systemic steroids

- Emergency care or hospitalization related to asthma or other chronic lung disease

- Systemic steroids for asthma exacerbation

7. History of diabetes mellitus (gestational diabetes is allowed if treatment was not
required postpartum and serum glucose is currently in the normal range)

8. History of coronary artery disease, arrhythmia, or congestive heart failure

9. Clinically significant ECG abnormality as determined by the Investigator

10. Poorly controlled hypertension (systolic blood pressure > 150 mmHg or diastolic blood
pressure > 95 mmHg) at Screening or predose on Day 1

11. History of anaphylaxis or angioedema

12. Known allergy to any of the ingredients in the vaccine formulation

13. Known allergy or sensitivity to latex

14. History of chronic rhinitis, nasal septal defect, cleft palate, nasal polyps, or other
nasal abnormality that might affect vaccine administration

15. Previous nasal surgery or nasal cauterization

16. Any symptoms of upper respiratory infection or temperature > 38°C within 3 days before
Day 1

17. Any symptoms within 24 hours before Day 1 of upper respiratory illness or allergy
flare-up that, in the opinion of the Investigator, presents as nasal congestion or
rhinorrhea that could inhibit the proper administration of the IP

18. Known or suspected malignancy, excluding non-melanoma skin cancers and other early
stage surgically excised malignancies that the Investigator considers to be
exceedingly unlikely to recur

19. Immunocompromised individuals, including those who have used corticosteroids
(including intranasal steroids), alkylating drugs, antimetabolites, radiation,
immune-modulating biologics, or other immunomodulating therapies within 90 days before
Day 1 or those who plan use during the study period

20. Use of statin medication within 30 days before Day 1 (see list in Section 6.8.1)

21. Receipt of intranasal medications (including over-the-counter medications) within 30
days before Day 1

22. Receipt of any IP within 30 days before Day 1

23. Receipt of any vaccine within 30 days before Day 1

24. Receipt of intranasal vaccine within 90 days before Day 1

25. Receipt of any licensed or investigational anthrax vaccine

26. Any change in medication for a chronic medical condition within 30 days before Day 1

27. Past regular use or current use of intranasal illicit drugs

28. Smokers, including smoking of any type (eg, cigarettes, electronic cigarettes,
marijuana). Prior smokers must have quit smoking at least 30 days before Day 1.

29. Any medical, psychiatric, or social condition or occupational or other responsibility
that in the judgment of the Investigator would interfere with or serve as a
contraindication to protocol adherence, assessment of safety (including
reactogenicity), or a subject's ability to give informed consent