Safety and Efficacy of VB-111 in Subjects With Advanced Differentiated Thyroid Cancer

Inclusion Criteria:

1. Histologically or cytologically confirmed advanced DTC (papillary, follicular, Hurthle
cell);

2. Absence of sensitivity to therapeutic radioiodine;

3. Measurable disease, defined as at least one non-bony lesion that can be accurately
measured in at least one dimension as confirmed with spiral CT scan

4. Life expectancy >3 months; ECOG performance status (PS) 0, 1, or 2; Karnofsky
performance status of ≥60%;

5. Subjects with a normal/acceptable hematological profile

6. Subjects with adequate renal function

Exclusion Criteria:

1. Presence of any of the following:

- Radiotherapy or chemotherapy <4 weeks prior to baseline visit; (Concurrent and/or
prior therapy with octreotide will be allowed, provided tumor progression on this
therapy has been demonstrated; Concurrent and/or prior therapy with
biphosphonates will be allowed)

- Radiotherapy to ≥25% of bone marrow;

2. Major surgery <4 weeks prior to baseline visit;

3. Any other ongoing investigational agents within 4 weeks before dosing;

4. Subjects who suffered from an acute cardiac event within the last 12 months, including
myocardial infarction, cardiac arrythmia, admission for unstable angina, cardiac
angioplasty, or stenting;

5. QTc prolongation (defined as QTc interval ≥500 msecs) or other significant ECG
abnormalities (e.g. frequent ventricular ectopy, evidence of ongoing myocardial
ischemia);

6. Subjects with active vascular disease, either myocardial or peripheral;

7. Subjects with proliferative and/or vascular retinopathy;

8. Subjects with known active liver disease (alcoholic, drug/toxin induced, genetic, or
autoimmune) other than related to tumor metastases;

9. Subjects with known CNS metastatic disease (Exception: Subjects with treated CNS
metastases stable by radiographic examinations >6 months after definitive therapy
administered, are eligible);

10. Subjects testing positive to one of the following viruses: HIV, HBV or HCV;

11. Any of the following conditions:

- Serious or non-healing wound, ulcer, or bone fracture;

- History of abdominal fistula, gastro-intestinal perforation, active
diverticulitis, intra-abdominal abscess or gastro-intestinal tract bleeding
within 6 months of dosing;

- Any history of cerebrovascular accident (CVA) within 6 months of dosing;

- Current use of therapeutic warfarin (Note: Low molecular weight heparin and
prophylactic low-dose warfarin [INR<1.2 X ULN] are permitted);

- History of bleeding disorder, including subjects with hemophilia, disseminated
intravascular coagulation (DIC), or any other abnormality of coagulation
potentially predisposing subjects to bleeding;

- Poorly controlled depression or anxiety disorder, or recent (within the previous
6 months) suicidal ideation;

12. Subjects with an ongoing requirement for immunosuppressive treatment, including the
use of glucocorticoids or cyclosporin, or with a history of chronic use of any such
medication within the last 4 weeks before dosing;

13. Uncontrolled intercurrent illness including, but not limited to ongoing or active
infection, or psychiatric illness/social situations that would limit compliance with
study requirements.