The purpose of this study is to determine whether ST266 will reduce pocket depth (PD) as an adjunctive to scaling and root planing (SRP) in subjects with moderate to severe periodontal disease.

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