Efficacy, Safety and Tolerability of AG013 in Oral Mucositis Compared to Placebo When Administered Three Times Per Day

This is a Phase 2, double-blind, placebo-controlled, 2-arm, multi-center trial in which
subjects will be randomized in a 1:1 ratio to receive either placebo or AG013. AG013 is a
mouth rinse formulation of Lactococcus lactis strain sAGX0085, deficient in the gene coding
for thymidylate synthase and producing human TFF1 (Trefoil Factor 1).

Approximately 200 subjects will be enrolled in the study. To protect subjects from
unanticipated safety risks, enrollment and treatment in the double-blind study will continue
until 10 subjects on AG013 have been recruited. The Data Safety Monitoring Board (DSMB) will
review safety data after these 10 subjects on AG013 have completed study treatment. If there
are no safety signals identified, the study will continue to recruit the planned number of
subjects.

There are 4 study periods as described below: screening, active treatment, short term
follow-up and long term follow-up. The screening phase will be no longer than 4 weeks. The
active treatment phase will be between 7 and 9 weeks depending on the subject's prescribed
CRT (chemoradiation therapy) plan. The short term follow-up phase will be 4 weeks in
duration. The long term follow-up will continue until 12 months post CRT. Oral mucositis (OM)
assessments will begin at the start of CRT and continue until the subject has completed short
term follow-up or until the OM resolves (as defined by a WHO (World Health Organization)
score of ≤ 1), whichever comes first. Long term follow-up will continue for 12 months to
assure that AG013 does not adversely impact the tumor response to anti-neoplastic therapy.

Inclusion Criteria:

1. Willing and able to understand and sign the study specific Informed Consent Form

2. Pathologically-confirmed squamous cell carcinoma of the oral cavity, oropharynx or
hypopharynx or HPV-positive unknown primaries presumed to be of oropharyngeal origin

3. Tumor HPV status established

4. Planned to receive either primary or post-operative CRT

5. Planned IMRT (Intensity-Modulated Radiotherapy)

6. Planned administration of cisplatin administered weekly or tri-weekly during RT

7. Males or females 21 years or older

8. Karnofsky performance score (KPS) ≥ 70%

9. Subjects of childbearing potential must agree to utilize effective contraceptive
methods of birth control during study participation and for 30 days following the last
treatment with IMP (Investigational Medicinal Product)

10. Screening laboratory assessments:

- Hemoglobin ≥ 10g/dl

- White blood count ≥ 3500 cells/mm3

- Absolute neutrophil counts ≥ 1500 cells/ mm3

- Direct bilirubin ≤ 2x upper limit of normal (ULN)

- Serum AST (aspartate aminotransferase) and ALT (alanine aminotransferase) ≤ 3 x
ULN

- Calculated Creatinine Clearance of 50 ml/min

- Pregnancy test (serum or urine): negative for females of childbearing potential:
a female is considered to be of child bearing potential unless she has had a
tubal ligation or is postmenopausal (without a menstrual period for at least one
year)

Exclusion Criteria:

1. Prior radiation to the head and neck

2. Presence of active infectious oral disease excluding oral candidiasis

3. Presence of any oral lesions that may confound the ability to assess oral mucositis
grade

4. Current use of antibiotic rinses or troches

5. Herbal, alternative remedies, and alcohol containing over-the-counter mouthwashes are
excluded during the course of the study

6. Current alcohol abuse syndrome

7. Chronic immunosuppression

8. Known seropositive for HIV

9. Use of investigational agent within 30 days of signing informed consent

10. Tooth extraction prior to radiation

11. Signs and symptoms of active dental disease

12. Female subjects who are pregnant or nursing

13. Any other clinical condition, psychiatric condition or prior therapy that, in the
opinion of the Investigator, would make the subject unsuitable for the study or unable
or to comply with follow-up visits