Phase 1 Trial of PAN-301-1 (SNS-301) in Cancer Patients

Human aspartyl-asparaginyl-β-hydroxylase (HAAH), also known as aspartate-β-hydroxylase, is an
~86 kDa type 2 transmembrane protein that belongs to the α-ketoglutarate-dependent
dioxygenase family. It is a highly conserved enzyme, which catalyzes the hydroxylation of
aspartyl and asparaginyl residues in epidermal growth factor-like domains of proteins
including Notch and homologs. HAAH was initially identified in a novel screen to identify
cell surface proteins up-regulated in liver cancer. It has subsequently been detected in a
diverse array of solid and blood cancers, including: liver, bile duct, brain, breast, colon,
prostate, ovary, pancreas, and lung cancers as well as leukemia. HAAH is not found in
significant quantities in normal tissue or in proliferative disorders.

The investigators have designed a bacteriophage lambda system to display HAAH peptides fused
at the C terminus of the head protein gpD of phage lambda. The phage carry 200-300 copies of
the gpD protein on their head and thus display many copies of an approximately 25 kDa
molecular weight fragment of HAAH on their surface. The drug substance is one of these HAAH
bacteriophage lambda constructs: HAAH-1λ (PAN-301-1).

This study evaluates the safety and immunogenicity of the PAN-301-1 vaccine in patients with
biochemically-relapsed prostate cancer.

Inclusion Criteria:

1. Signed and dated written Ethics Committee approved informed consent

2. Men aged 21 to 70 years with a histologic diagnosis of prostate cancer with a
biochemical relapse following definitive local therapy (RP or radiation therapy)

3. Patients are not eligible or are unwilling to receive additional definitive therapy
following relapse (either RP or radiation therapy)

4. No prior cytotoxic chemotherapy for the current cancer

5. Normal electrocardiogram (ECG) or ECG with no clinically significant findings as
determined by the Principal Investigator

6. Presence of biochemically relapsed prostate cancer defined as either: 1) PSA > 2 ng/mL
1 year following initial definitive treatment for prostate cancer: or, 2) PSA doubling
time (greater than 0.4 ng/mL) < 12 months; or, 3) PSA velocity > 2 ng/mL/year at any
time following radical prostatectomy or radiation therapy.

7. Positive expression of HAAH in either archived tumor tissue or serum

8. No clinical or radiologic evidence of distant metastatic disease as measured by pelvic
MRI or CT scan in addition to bone scan. These studies will need to be performed
within 28 days prior to the start of the study.

9. No history of immunosuppressive disease

10. No evidence of active autoimmune disease. Active autoimmune disease is defined as any
disease process that has specifically needed administration of immune suppressive and
or cytoreductive therapy currently or within the last 1 year.

11. Able and willing to comply with all study procedures

Exclusion Criteria:

1. PSA doubling time of < 3 months

2. Participation in a clinical trial within 30 days prior to enrollment

3. Prior major surgery or radiation therapy within 4 weeks of enrollment

4. Any illness or condition that in the opinion of the Investigator may affect the safety
of the subject or the evaluation of any study endpoint

5. Screening blood counts of the following:

Hematopoietic: absolute neutrophil count < 1500/μL, Platelets < 100,000/μL, hemoglobin
< 9 g/dL; Liver/Metabolic: alanine aminotransferase (ALT) and aspartate transaminase
(AST) > 2.5 × upper limit of the normal reference range (ULN), total bilirubin >2 ×
ULN, albumin < 2.8 g/dL; Renal: creatinine clearance < 50 mL/min as predicted by the
Cockcroft-Gault formula.

6. Subjects whose partners are WOCBP must use an adequate method of birth control while
on study drug and at least for 3 weeks after discontinuation of study drug

7. Current or anticipated concomitant immunosuppressive therapy (excluding non-systemic
inhaled, topical skin and/or eye drop containing corticosteroids)

8. Any concurrent condition requiring the continued use of systemic steroids (see above)
or the use of immunosuppressive agents including methotrexate. All other systemic
corticosteroids must be discontinued at least 4 weeks prior to first study treatment

9. Receipt of any blood product within 1 month of enrollment

10. Receipt of any vaccine within 4 weeks of enrollment

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

12. Been imprisoned or compulsorily detained (involuntarily incarcerated) for treatment of
either a psychiatric or physical (i.e. infectious disease) illness

13. Patients who have a history of coagulopathies, thrombosis or who are receiving active
anticoagulation for any condition, such as but not limited to, artificial heart
valves, atrial fibrillation, etc.

14. Any other conditions judged by the Investigator that would limit the evaluation of a
subject