Phase 2, Open-Label Study for Safety, Microbiology and PK of Single or Multiple Oral C16G2 Gel Doses

Open-label, multiple arm, safety, microbiology and pharmacokinetic (PK) study in healthy
adult male and female subjects 18-75 years of age conducted in two parts.

Part A of the study will evaluate up to 6 study arms, depending on the microbiology response
evaluated. Before dosing of C16G2, eligible subjects will undergo professional dental
prophylaxis on Day 0. Clinic visits for all Study Arms include Visit 1 (Screening/Days -21 to
0), Treatment Visits 2 through 6 (Baseline/Day 0 through Day 4), and follow-up Visits 7
through 11 (Day 5, 8, 12, 19 ± 1 and 33 ± 2).

All subjects will be assessed for safety and microbiology parameters for approximately 5
weeks. A subset of subjects in Study Arms 2 and 4 will be assessed for pharmacokinetic
parameters. Part A of the study is no longer enrolling study subjects.

Part B of the study will evaluate up to 5 study arms, depending on the microbiology response
evaluated during 2 interim microbiology reviews. Clinic visits for all study arms except
Study Arm 5 include Visit 1 (Screening/Days -21 to 0), Visit 2 (Baseline/Day 0), Visits 3
through 17 (Days 1 through 6, morning and evening visits, and Days 7, 10 and 14). All
subjects will be assessed for safety and microbiology parameters for approximately 2 weeks.
Before dosing of C16G2, eligible subjects will undergo professional dental prophylaxis on Day
0. Study drug will be administered for 7 consecutive days. The Sponsor will perform a
microbiology review to evaluate the S. mutans response in Study Arms 1 & 2 and, if
applicable, in Study Arms 3a or 3b. In Study Arm 5, subjects will receive multiple C16G2
doses on a single day and will be evaluated for safety, microbiology and pharmacokinetic
parameters. Clinic visits for Study Arm 5 will include Visit 1 (Screening/Days -21 to 0),
Visit 2 (Baseline/Day 0), Visit 3/Day 1 and Visit 4/Day 6.

Inclusion Criteria (Parts A & B):

1. Males and females, 18-75 years of age, inclusive, at the time the Informed Consent
Form is signed

2. Female subjects of childbearing potential, defined as not surgically sterile, 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, monogamous
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

5. Have a minimum of six unrestored bicuspids and molars with ≤50% of molars and
bicuspids having restorations, crowns, sealants or are missing

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

7. Have a salivary S. mutans of 2.0 x 10^4 CFUs/mL or greater (Part A) or 1.0 x 10^5
colony forming unit (CFU)/mL or greater (Part B) 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 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. Able to understand and sign the Informed Consent Form prior to initiation of study
procedures

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

Exclusion Criteria (Parts A & B):

1. Advanced periodontal disease

2. Active caries lesion(s) within 30 days prior to study drug administration (confirmed
by dental examination and standard radiographs)

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 or partial dentures, or orthodontic appliances, e.g., night guards, permanent
retainers

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

7. Medical history indicating the woman is pregnant, breastfeeding/ lactating or she 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