Safety and Efficacy Study of TVGV-1 Vaccine to Treat HPV Induced Cervical HSIL

The purpose of the Phase 2a Study VAX 02-01 is to assess the safety and activity of TVGV-1
vaccine construct in achieving the absence of histologic HSIL (CIN2/3) (regression to LSIL or
less) as assessed by biopsy at last study Visit 11, Day 270.

The objective of the TVGV-1 program is to develop a non-surgical alternative that is
reliable, safe, and would avoid potential surgical risks such as preterm birth, perinatal
mortality, risk of infertility, incontinence and disfigurement, as well as reduced cost and
inconvenience for an otherwise economically productive young subject population.

Inclusion Criteria:

1. Female age 18 to 55 years

2. Written informed consent in accordance with institutional guidelines

3. Negative pregnancy test (urine and blood tests)

4. Women of child bearing potential must agree to use contraception through one menstrual
cycle post end of study or if early withdrawal, through what would have been visit 11.
Methods include intrauterine device or double barrier method, hormonal contraceptive
in combination with a double barrier method.

5. Patients who have ONLY HPV 16 OR HPV 16 AND 18 and no other High-Risk HPV by Cobas
test will be included.

6. Histologically confirmed, positive HSIL of CIN2+ or higher (only CIN2+/3 subjects will
be selected) cervical biopsy, confirmed by external (independent) pathologist panel
within the 12 weeks prior to enrollment. If the standard care biopsy is not available
for evaluation by the independent pathologist, a fresh biopsy and endocervical
curettage will be required. The extent of colposcopic HSIL disease should not involve
more than two quadrants of the cervix. Biopsies should be taken from each affected
quadrant

7. Adequate visualization of entire cervix, cervical lesion(s) and squamous-columnar
junction

8. Normal electrocardiogram (ECG), laboratory values (chemistry, complete blood count)
and urinalysis, as judged Grade 0-1 by per National Cancer Institute Common Toxicity
Criteria (NCI-CTC)

9. Agrees to Loop Electrosurgical Excision Procedure (LEEP), Cold Knife Conization (CKC)
or Hysterectomy being performed at the end of study according to the standard-of-care

Exclusion Criteria:

1. History of cancer (excluding basal cell carcinoma of the skin) including cervical
cancer

2. Eastern Cooperative Oncology Group (ECOG) performance status >2 (See Appendix G)

3. Administration of any blood product within 3 months of enrollment

4. Active infection requiring antimicrobial treatment that would interfere with
interpretation of adverse events, cutaneous reactions or efficacy. Treatment of minor
concurrent infections should be limited to less than 10 days.

5. Administration of any vaccine within 8 weeks of enrollment and within 4 weeks for flu
vaccine.

6. Participation in any study with an investigational compound or device within 30 days
prior to signing informed consent

7. Any hematologic disorder involving platelets or clotting abnormalities or any
condition requiring treatment with transfusions, anticoagulants except platelet
inhibitors (NSAIDs as needed for pain are permitted)

8. Active drug or alcohol use or dependence that, in the opinion of the Site
Investigator, would interfere with adherence to study protocol

9. Skin conditions that require consistent use of topical corticosteroids or other local
or systemic therapy that may interfere with interpretation or description of
skin-related adverse events linked to vaccination

10. The standard criteria for prospective clinical trials of medications developed by
Drug-Induced Liver Injury Network (established by The National Institute of Diabetes
and Digestive and Kidney Diseases) will be used to assess the laboratory test
abnormalities. Normal range for these labs will typically be 5 - 40 IU/L for AST; 7 -
56 IU/L for ALT; 0.2 - 1.2 mg/dL for bilirubin. Subjects will be excluded if values
are x 2-x 2.5 the upper limit

11. Evidence of hematopoietic, cardiovascular, hepatic, renal, neurologic, psychiatric,
dermatologic, immune disorder, or other disease that may interfere with assessment of
safety or efficacy of vaccine activity as indicated in study objectives

12. Any known allergic reaction to vaccine components

13. Any other medical condition(s) that, in the judgment of the Site Investigator, might
interfere with the study or require treatment that might interfere with the study

14. Family member of the investigation study staff

15. Pregnant or breast-feeding

16. Inability to provide informed consent

17. A subject with a history or expectation of noncompliance with medications or treatment
protocol

18. Receipt of (e.g. Gardasil® or Cervarix®) HPV preventative vaccines within 8 years of
study enrollment

19. Excessive use of acetaminophen or other potentially hepatotoxic drugs