A Study of Ad-RTS-hIL-12 With Veledimex in Subjects With Glioblastoma or Malignant Glioma

Eligible patients will be stratified to one of two groups, according to clinical indication
for tumor resection. Patients who are scheduled for a standard of care craniotomy and tumor
resection will receive one dose of veledimex before the resection procedure. Ad-RTS-hIL-12
will be administered by free-hand injection. Patients will continue on oral veledimex for 14
days.

Patients not scheduled for tumor resection will receive Ad-RTS-hIL-12 by stereotactic
injection and then will continue on oral veledimex for 14 days.

The study is divided into three periods: the screening period, the treatment period and the
follow-up period.

Inclusion Criteria:

1. Male or female subjects ≥ 18 and ≤ 75 years of age

2. Provision of written informed consent for tumor resection, stereotactic surgery, tumor
biopsy, samples collection and treatment with investigational products prior to
undergoing any study procedures

3. Histologically confirmed supratentorial glioblastoma or other WHO grade III or IV
malignant glioma from archival tissue.

4. Evidence of tumor recurrence/progression by MRI (RANO criteria) post standard initial
therapy.

5. Previous standard of care anti-tumor treatment including surgery and/or biopsy and
chemoradiation. The washout periods from prior therapies are intended as follows:

1. Nitrosoureas: 6 weeks

2. Other cytotoxic agents: 4 weeks

3. Anti-angiogenic agents including bevacizumab: 4 weeks

4. Targeted agents including small-molecule tyrosine kinase inhibitors: 2 weeks

5. Experimental immunotherapies: 3 months

6. Vaccine based therapy: 3 months

6. Able to undergo standard MRI scans with contrast agent

7. Karnofsky Performance Status ≥ 70

8. Adequate bone marrow reserves and liver and kidney function, as assessed by the
following laboratory requirements:

1. Hemoglobin ≥ 9 g/L

2. Lymphocytes > 500/ mm3

3. Absolute Neutrophil Count ≥ 1500/ mm3

4. Platelets ≥ 100,000/ mm3

5. Serum creatinine ≤ 1.5 x ULN

6. AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN. For subjects with documented liver
metastases, ALT and AST ≤ 5 × ULN

7. Total bilirubin < 1.5 x ULN

8. International Normalized Ratio (INR) and activated Partial Thromboplastin Time
[PTT] within normal institutional limits

9. Male and female subjects must agree to use a highly reliable method of birth control
(expected failure rate less than 5% per year) from the screening visit through 28 days
after the last dose of study drug. Women of childbearing potential must have a
negative pregnancy test at screening.

Exclusion Criteria:

1. Radiotherapy within 4 weeks or less prior to starting first veledimex dose

2. Subjects with clinically significant increased intracranial pressure or uncontrolled
seizures.

3. Known immunosuppressive disease, autoimmune conditions, and /or chronic viral
infections

4. Use of systemic antibacterials, antifungals or antivirals for the treatment of acute
clinically significant infection within 2 weeks of first veledimex dose. Concomitant
therapy for chronic infections is not allowed. Subjects must be afebrile prior to
Ad-RTS-hIL-12 injection; only prophylactic antibiotic use is permitted
perioperatively.

5. Use of enzyme-inducing anti-epileptic drugs (EIAED) within 7 days prior to the first
dose of study drug.

6. Other concurrent clinically active malignant disease, requiring treatment, with the
exception of non-melanoma cancers of the skin or carcinoma in-situ of the cervix or
non-metastatic prostate cancer.

7. Nursing or pregnant females

8. Prior exposure to veledimex

9. Use of medications that induce, inhibit or are substrates of CYP450 3A4 within 7 days
prior to the first veledimex dosing

10. Presence of any contra-indication for a neurosurgical procedure

11. Unstable or clinically significant concurrent medical condition that would, in the
opinion of the investigator or medical monitor, jeopardize the safety of a subject
and/or their compliance with the protocol.