Safety, Efficacy and Treatment Regimen Study of ST266 in Subjects With Moderate to Severe Periodontitis

The study is a 9-month, randomized, double-blind, parallel-design study of subjects with
existing moderate to severe periodontal disease randomly assigned to one of three groups. The
primary endpoint of PD change will be evaluated following 9 months of treatment. Subjects
will be followed for 9 months for safety and radiographic evaluations.

Subjects who meet inclusion criteria will be randomized to one of three treatment groups.

Randomization will be stratified by site and smoker status (never smoked or quit smoking more
than two years ago vs. has smoked within the last two years). Randomization will be blocked
such that assignment to treatment groups both within sites and within smoker status will be
approximately even (1:1:1). Treatment will be initiated after SRP.

All subjects will be evaluated at baseline and Days 1, 15, 30, 60, 90, 180, and 270.

Inclusion Criteria:

- Provision of signed, written informed consent prior to participation in any
study-related procedures.

- Good general health as evidenced by medical history.

- Between 18 and 85 years of age at time of informed consent signature.

- Male or female.

- Minimum of 18 teeth, excluding third molars.

- Having moderate to severe periodontal disease according to AAP definition (at least 6
teeth ≥6 mm PD and ≥3 mm CAL at baseline).

- Having >30 percent bleeding sites upon probing.

- Willing to abstain from chewing gums and other mouth rinses for the study duration.

- Ability and willingness to attend all study visits and comply with all study visits
and comply with all study procedures and requirements.

- Willingness to abstain from routine dental care.

- For women with reproductive potential, willingness to use highly effective
contraception (e.g. licensed hormonal contraception, intrauterine device, abstinence,
or vasectomy in partner).

Exclusion Criteria:

- Presence of orthodontic appliances.

- A soft or hard tissue tumor of the oral cavity.

- Any dental condition that requires immediate treatment, such as carious lesions.

- Participation in any other clinical study within 30 days of screening or during the
study.

- Pregnancy or lactation. If a subject meets this criterion, she may be rescreened for
study participation when she no longer meets this criterion.

- Antibiotic therapy within the last 30 days.

- Chronic use (≥3 times/week) of anti-inflammatory medications (e.g., non-steroidal anti
inflammatory drugs, steroids). Low-dose aspirin (less than 325 mg daily) is allowed.

- Immunocompromised subjects.

- Subjects with cancer or a history of cancer within the last 5 years of screening.

- Any medical history or any concomitant medication that might affect the assessment of
the study treatment or periodontal tissues, such as diabetes, nifedipine, phenytoin
(Dilantin), or anticoagulant medications (e.g., warfarin [Coumadin] etc.).

- Involvement in the planning or conduct of the study.

- History of any clinically significant disease or disorder which, in the opinion of the
investigator, may either put the subject at risk because of participation in the
study, or interfere with interpretation of the subject's study results.

- Previous randomization for treatment in the present study