A Study to Evaluate the Microbiology, Safety and Tolerability of C16G2 Dental Strip Application

A single-blind, randomized, placebo-controlled, phase 2 study to evaluate oral microbiology
and safety of multiple C16G2 Strip applications in male and female dental subjects 12-75
years of age.

The study will compare multiple study drug administrations of 9.2 mg, 18.4 mg, and 36.8 mg
C16G2 Strip or Placebo in Study Arms 1 through 3, respectively. Enrollment of subjects in
Study Arms 1 through 3 will occur sequentially in an ascending dose-escalation manner. Before
dosing of study drug, eligible subjects will receive professional dental prophylaxis between
Days -7 and -2. Subjects will receive 11 doses administered over approximately two weeks.
Each subject will receive a single dose on Day 0, followed by 5 days of AM and PM dosing
starting on Day 7. To evaluate the durability of S. mutans suppression, study subjects will
be followed for microbiology for up to 1 month after the last study drug administration.

Clinic visits include Visit 1 (Screening/Days -30 to -1), Visit 2 (Prophylaxis/Day -7 to -2),
Eligibility Confirmation & Baseline Visit 3, Follow-up Visits 4-7 (Safety and Microbiology),
Visits 8-17 (Study Drug Administration), Follow-up Visits 18-20 (Safety and Microbiology) and
Follow-up Visits 21-22 (Microbiology only).

Inclusion Criteria:

1. Males and females, 12-75 years of age

2. Adults subjects provide written informed consent and adolescent subjects give written
or verbal assent, as appropriate, and parent(s) or legal guardian(s) give written
informed consent

3. Female subjects of childbearing potential must agree to use one of the following forms
of contraception from screening through the last study visit: hormonal (oral, implant,
or injection) begun >30 days prior to screening; barrier (condom, diaphragm, or
cervical cap with spermicide); intrauterine device (IUD). Acceptable contraceptive
options may also include abstinence, relationship with a same sex partner or partner
who has had a vasectomy at least six (6) months prior to the screening visit

4. Negative urine pregnancy test in all females of childbearing potential (past menarche)

5. Male subjects of sexual activity age: willing to use contraception or abstain from
sexual activity beginning with the first exposure to study drug and continuing until
discharged from the study due to completion or Early Termination

6. Healthy, as determined by the Investigator (in consultation with the Medical Monitor,
as needed), based on medical and dental history, concurrent illnesses, laboratory
results, concomitant medications, oral cavity assessment, and targeted physical
examination (general, extraoral, head and neck) during Screening Note: Subjects on a
stable dose of medication may be eligible for screening and will be assessed by the
medical monitor on a case-by-case basis.

7. Have a minimum of 12 bicuspids and molars with a minimum of 8 molars and bicuspids NOT
having restorations, crowns or sealants

8. Demonstrated ability to expectorate ≥2 mL of stimulated saliva in 5 minutes

9. Have a salivary S. mutans of 1.0 x 10^5 CFUs/mL or greater at Screening using mitis
salivarius-bacitracin (MSB) agar plating

10. Willing to refrain from using non-study dentifrice and other non-study oral care
products (oral care rinses, fluoride products, etc.) during the study

11. Willing to postpone elective dental procedures (e.g., dental cleanings) between
Screening and final post-treatment visit (End of Study or Early Termination)

12. Willing and able to comply with oral hygiene and diet instructions

13. Able to communicate with the Investigator/study center personnel, understand and
comply with the study requirements, and willing to return for protocol-specified
visits at the appointed times

Exclusion Criteria:

1. Advanced periodontal disease

2. Active caries lesion(s) within 30 days prior to study drug administration (confirmed
by comprehensive caries examination including standard radiographs). Subjects
presenting with insipient, non-cavitated lesion(s) are not excluded Note: If
radiographs are deemed appropriate for the study and taken within 6 months prior to
the Screening visit, these may be used for determining eligibility and are not
required to be repeated at Screening

3. Partially erupted teeth where the entire crown is not erupted or an operculum is
present

4. Medical condition (e.g., artificial heart valve, history of infective endocarditis,
cardiac transplant with valvular dysfunction, congenital heart disease or total joint
replacement) for which antibiotics are recommended prior to dental visits and/or
procedures

5. Pathologic lesions of the oral cavity (suspicious or confirmed)

6. Full dentures or permanent orthodontic appliances, e.g., braces, buccal or lingual
brackets.

7. Use of systemic antibiotics, topical oral antibiotics, or use of other drugs, which in
the opinion of the Investigator could influence the study outcome, beginning 30 days
prior to Screening until the end of study participation

8. Medical history indicating the woman is pregnant, breastfeeding/lactating or has a
positive urine pregnancy test

9. Participation in a clinical trial or receipt of a non-FDA approved therapy within 30
days prior to study drug administration (depending on the specifics, participation in
an observational study is not necessarily excluded)

10. Presence of any condition or concurrent illness, which in the opinion of the
Investigator, would compromise normal immune function (e.g., diabetes, rheumatoid
arthritis, lupus, liver disease, organ transplant, etc.), interfere with the use of
study dentifrice and oral care products, or interfere with the ability to comply with
study requirements, or jeopardize the safety of the subject or the validity of the
study results