A Phase 1 Open-Label, Dose Escalation Study to Determine the Optimal Dose, Safety, and Activity of AAV2hAQP1 in Subjects With Radiation-Induced Parotid Gland Hypofunction and Xerostomia

Inclusion Criteria:

   1. Male or female subjects ≥18 years of age.

   2. History of radiation therapy for head and neck cancer.

   3. Abnormal parotid gland function as judged by both absence of unstimulated parotid
   salivary flow and a stimulated parotid salivary flow in the targeted parotid gland >0
   and <0.3 mL/min/gland after 2% citrate stimulation.

   4. No evidence of recurrence of the primary malignancy by an otolaryngology (ears, nose,
   and throat [ENT]) assessment. Additionally, all subjects must be disease-free of head
   and neck cancer for at least 5 years following the end of treatment at screening, with
   the exception of subjects with a history of HPV+ OPC (base of tongue, oropharynx,
   pharynx, soft palate, tonsil) who must be disease free for at least 2 years following
   the end of treatment. Disease status will be determined by negative clinical
   examinations and computed tomography (CT) scans of the neck and chest. If subjects
   have had a magnetic resonance imaging (MRI) of the neck or a positron emission
   tomography (PET) scan within 6 months of screening, then a CT scan is not required,
   except for HPV+ OPC subjects who must have scans at 2 years post treatment.

   5. Female subjects of childbearing potential (i.e., ovulating, pre-menopausal, and not
   surgically sterile) and all male subjects must use a medically accepted contraceptive
   regimen during their participation in the study and until all samples collected at 2
   consecutive visits following AAV2hAQP1 administration are negative. Acceptable methods
   of contraception for male subjects include the following:

      - Condoms with spermicide. Acceptable methods of contraception for female subjects
      include the following:

      - Intrauterine device for at least 12 weeks prior to Screening.

      - Hormonal contraception (oral, implant, injection, ring, or patch) for at least 12
      weeks prior to Screening.

      - Diaphragm used in combination with spermicide.

Exclusion Criteria:

   1. Pregnant or lactating women or women planning to become pregnant.

   2. Any experimental therapy within 3 months before Day 1.

   3. Active infection that requires the use of intravenous antibiotics and does not resolve
   at least 1 week before Day 1.

   4. Uncontrolled ischemic heart disease (i.e., unstable angina, evidence of active
   ischemic heart disease on electrocardiogram [ECG]).

   5. History of systemic autoimmune diseases affecting the salivary glands.

   6. Use of systemic immunosuppressive medications (i.e., corticosteroids).

   o Note: Topical, inhaled, or intranasal corticosteroids are allowed.

   7. Malignancy, other than head and neck cancer, within the past 3 years, with the
   exception of adequately treated basal cell or squamous cell carcinoma of the skin or
   in situ cervical carcinoma.

   8. Active infections including, Epstein-Barr virus (EBV), cytomegalovirus (CMV),
   hepatitis B (HBV), hepatitis C (HCV), or human immunodeficiency virus (HIV) infection.

   9. White blood cell count <3000/μL, absolute neutrophil count <1500/μL, hemoglobin <10.0
   g/dL, platelet count <100,000/μL, or absolute lymphocyte count ≤500/μL.

10. Alanine aminotransferase and/or aspartate aminotransferase >1.5 × the upper limit of
   normal (ULN), alkaline phosphatase >1.5 × ULN, or total bilirubin >1.5 × ULN with any
   elevation of liver enzymes.

11. Estimated glomerular filtration rate <60 mL/min/1.73 m2 using the Modification of Diet
   in Renal Disease equation.

12. Active use of tobacco products as determined by self-reporting.

13. Allergy to iodine or shellfish, and thus unable to have sialographic evaluations.

14. Allergy or hypersensitivity to glycopyrrolate.