Phase 2 Study to Evaluate the Microbiology and Safety of C16G2 Administered to Adult and Adolescent Dental Subjects

This multi-center, multiple-arm study will evaluate the microbiological activity and safety
of C16G2 Gel in male and female dental subjects, 12 to 75 years of age. The study will be
conducted in a randomized, double-blind, placebo-controlled and open-label manner and enroll
adolescent (12-17 years of age) and adult subjects (18-75 years of age).

A total of approximately 128 study subjects will be enrolled into up to 7 study arms. Study
drug (C16G2 Gel or Placebo) will be administered via manual brush gel application (MBGA) or
tray gel application (TGA). Two C16G2 concentrations will be evaluated. Four study arms will
be conducted in a double blind manner, with a treatment allocation ratio of 4:1
(C16G2:Placebo), three study arms will be conducted in an open-label manner. Before dosing,
eligible subjects will undergo professional dental prophylaxis on Day 0. Clinic visits for
all study arms will include Visit 1 (Screening/Days -21 to 0), and a varying number of dosing
and follow-up visits.

Inclusion Criteria:

1. Males and females, 12-75 years of age, inclusive, at the time the Assent and/or
Informed Consent Form is signed

2. Female subjects of childbearing potential, defined as not surgically sterile or at
least two (2) years postmenopausal, 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 same sex partner or partner who has had a
vasectomy at least six (6) months prior to the screening visit

3. Male subjects only: 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

4. 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 (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.

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

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

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

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

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

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

11. Has dentition adequate for custom dental tray gel application

12. Able to understand and sign the Assent and/or Informed Consent Form prior to
initiation of study procedures

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 if deemed necessary
by the Investigator) Note: Subjects presenting with insipient, non-cavitated lesion(s)
are not excluded

3. 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

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

5. Full dentures or orthodontic appliances, e.g., braces; Note: partial dentures,
removable retainers and night guards are not excluded, provided that they are cleaned
regularly throughout the duration of the study.

6. Use of systemic antibiotics, topical oral antibiotics, or use of other drugs, which in
the opinion of the Investigator could influence the study outcome, within 30 days
prior to Screening and throughout the entire study.

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

8. 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)

9. Prior participation in a C16G2 clinical trial and known to have received C16G2 active
gel or mouth rinse Note: Placebo subjects are not 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