Phase I Study of INO-1800 With or Without INO-9112 + EP in Chronic Hepatitis B Subjects

INCLUSION CRITERIA:

- Chronic Hepatitis B virus infection

- Negative for Hepatitis A IgM, C, D and HIV

- Liver biopsy, Fibroscan® or equivalent elastography-based test obtained within the
past 6 mon demonstrating liver disease without evidence of bridging fibrosis or
cirrhosis supported by platelet count greater than the central laboratory LLN at
screening

- Positive for Hepatitis B surface antigen (≥250 IU/mL at screening)

- Nucleos(t)ide treatment for at least 1 year with ongoing nucleos(t)ide analogue
treatment at randomization

- HBV DNA <90 IU/mL for ≥6 mon prior to randomization

- Screening laboratory values within normal range

- ALT ≤1.5x ULN from 2 measurements separated by at least 14 days during the 6 mon prior
to randomization and ALT at screening ≤1.5x ULN

- AST, TBili, DBili, GGT, Alk Phos and albumin within normal range or judged to be not
clinically significant by PI and medical monitor at screening

- For men and women who are not postmenopausal [i.e. ≥ 12 months of non-therapy-induced
amenorrhea, confirmed by follicle stimulating hormone (FSH), if not on hormone
replacement] or surgically sterile (vasectomy in males or absence of ovaries and/or
uterus in females) agreement to remain abstinent or use 1 highly effective or combined
contraceptive methods that result in a failure rate of < 1% per year during the
treatment period and at least through week 12 after last dose

EXCLUSION CRITERIA:

- Pregnant or breastfeeding females

- Positive serum pregnancy test at screening or positive urine pregnancy test at
randomization

- Use of topical corticosteroids at or near the intended administration site

- Autoimmune disorders, transplant recipients, other immunosuppression including any
concurrent condition requiring the use of immunosuppressive/immunomodulating agents
(eye drop-containing and infrequent inhaled corticosteroids are permissible)

- Need for systemic antiviral treatment (other than for chronic hepatitis B infection)

- Documented history or other evidence of decompensated liver disease (e.g., ascites,
bleeding from esophageal varices, Child-Pugh clinical classification B or C)

- History of liver cirrhosis demonstrated by biopsy, Fibroscan® or equivalent
elastography-based test

- History of other evidence of a medical condition associated with chronic liver disease
[e.g., hemochromatosis, autoimmune hepatitis, alcoholic liver disease, non-alcoholic
steatohepatitis (NASH), toxin exposure, thalassemia, etc.]

- Documented history or other evidence of metabolic liver disease within 1yr of
randomization

- Abnormal renal function including serum creatinine >ULN or calculated creatinine
clearance <70 mL/min (using the Cockcroft Gault formula)

- History of or suspicion of HCC

- Screening alpha fetoprotein ≥13 ng/mL

- Prior history or current malignancy other than adequately treated BCC, unless history
of BCC is near intended administration site

- History of significant medical conditions [e.g., cardiac (including ventricular or
supraventricular arrhythmias), renal disease, pulmonary, gastrointestinal,
neurological]

- Significant acute infection (e.g., influenza, local infection) or any other clinically
significant illness within 2 weeks of randomization

- Administration of any blood product within 3 mon of randomization

- History of seizures (unless seizure free for 5yrs)