Open- Label Trial of Sipuleucel-T Administered to Active Surveillance Patients for Newly Diagnosed Prostate Cancer

The ProVent Study is designed to look at subjects who recieve sipuleucel-T compared to
control subjects followed on AS. The study will enroll subjects being followed by AS and
initially diagnosed within 12 months prior to Screening with either ISUP Grade Group 1 or 2
adenocarcinoma of the prostate.

The Screening Phase will begin at the completion of the informed consent process and
continues until randomization. After Screening assessments are completed, eligible subjects
will be randomized 2:1 to the sipuleucel-T arm or the control arm. Subjects randomized to
sipuleucel-T arm will receive product as described in the sipuleucel-T approved label.

Subjects will undergotheir first leukapheresis within 60 days of randomization.

Subjects randomized to the control arm will be followed on AS. The Active Phase will begin at
randomization and continues through completion of the end of Active Phase study visit (within
30 days of Biopsy 2). Once a subject from either the sipuleucel-T or control arms completes
the end of Active Phase visit, they will enter the Follow-up Phase and complete Follow-up
Phase visits every 6 months starting from their last Active Phase visit. The Follow-up Phase
visits end when the last subject enrolled completes Biopsy 2 and end of Active Phase visit or
until the study is terminated by the sponsor.

Inclusion Criteria:

- 1. Age is ≥ 18 years

- 2. Written informed consent provided prior to the initiation of study procedures

- 3. Histologically proven adenocarcinoma of the prostate initially diagnosed ≤12 months
of Screening. All biopsy slides with subject information redacted must be submitted
for BICR.

- 4. Prostate cancer diagnosis determined by BICR as one of the following:

1. ISUP Grade Group 1 with 3 or more cores positive from a systematic (≥10 cores)
biopsy

2. ISUP Grade Group 1 with ≥ 1 core positive with ≥50% cancer involvement from a
systematic (≥10 cores) biopsy

3. ISUP Grade Group 1 from 3 or more positive cores from any combination of cores
from a systematic (≥10 cores) biopsy and MRI targeted biopsy (note: multiple
cores from each MRI targeted lesion will count as 1 core)

4. ISUP Grade Group 1 from a negative systematic (≥10 cores) biopsy and an MRI
targeted core positive with ≥50% cancer involvement

5. ISUP Grade Group 2 from a systematic (≥10 cores) biopsy with <50% of the total
number of any cores positive for cancer

6. ISUP Grade Group 2 from a negative systematic (≥10 cores) biopsy and MRI targeted
core(s) positive for Gleason 3+4 (see note below)

7. ISUP Grade Group 2 from any combination of cores from a systematic (≥10 cores)
biopsy and MRI targeted biopsy (see note below)

Note for f and g: the total number of positive cores must be <50% of total cores from both
the systematic biopsy and MRI targeted lesions; each MRI targeted lesion, irrespective of
multiple positive cores, will each count as 1 core for the total number of positive cores,
e.g., 4 targeted lesions with 2 positive cores each will only add 4 to the total core
count.

- 5. Subject consents to standard of care for biopsy frequency of 2 on-study prostate
biopsies and to provide biopsy tissue for study endpoint analysis.

- 6. Estimated life expectancy ≥ 10 years

- 7. Candidate for primary curative therapy (e.g., surgery or radiation) if prostate
cancer progression occurs

- 8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

- 9. Adequate baseline hematologic, renal, and liver function tests as evidenced by
laboratory test results within the following ranges ≤30 days prior to randomization
White blood cell (WBC) count ≥ 3.0 x 10^6 cells/mL Absolute neutrophil count (ANC) ≥
1.5 x 10^6 cells/mL Platelet count ≥ 1.0 x10^5 cells/uL Hemoglobin (Hgb) ≥ 10.0 g/dL
Creatinine ≤ 1.5 mg/dL Total bilirubin ≤ 1.5 x upper limit of normal (ULN) Alanine
aminotransferase (ALT) ≤ 2.0 x ULN Aspartate aminotransferase (AST) ≤ 2.0 x ULN

Exclusion Criteria:

- 1. Former therapy for prostate cancer (local or systemic)

- 2. Any previous prostatic surgical procedure that significantly changes the anatomy of
prostate (at the discretion of sponsor's Medical Monitor)

- 3. Any investigational product received for prostate cancer

- 4. Prostate biopsy specimen reveals neuroendocrine or small cell features

- 5. Primary Gleason score is ≥ 4 or any Gleason pattern 5

- 6. Any evidence of locally advanced, regional or metastatic disease, including
regional and distant lymph node enlargement (Nodes ≥1.5 cm in the short axis are
considered pathologic and measurable)

- 7. A history of a cerebrovascular event (CVE) or transient ischemic attack (TIA)

- 8. Subject has used a 5-alpha-reductase inhibitor (e.g., finasteride or dutasteride)
continuously for ≥ 6 months and within 6 months prior to study Screening

- 9. Subject has a history of any other stage I-IV malignancy, except for basal or
squamous cell skin cancer. The subject must be disease free and off any
malignancy-related treatment for at least 5 years.

- 10. Subject has prior use within 30 days of study Screening of any herbal, dietary, or
alternative anti-cancer treatment or product, such as PC-SPES (or PC-x product), saw
palmetto, ketoconazole, an estrogen-containing nutraceutical, or high dose calcitriol
(>0.5 μg/day). The Investigator will consider herbal therapies on a case-by-case basis
to determine whether they fall into the category of prohibited medications based on
their potential for hormonal or anti-cancer or anti-cancer properties.

- 11. Need for systemic chronic immunosuppressive therapy (e.g., anti-tumor necrosis
factor alpha monoclonal antibodies, glucocorticoids)

- 12. Uncontrolled, concurrent illness including, but not limited to the following:
ongoing or active infection (bacterial, viral, or fungal), symptomatic congestive
heart failure (New York Classification III-IV) or unstable angina pectoris within the
last 6 months, or psychiatric illness that would limit compliance with study
requirements as well as any condition that would preclude a subject from undergoing
leukapheresis (e.g., within the previous 6 months: myocardial infarction,
interventional cardiology procedure such as angioplasty or stent placement, pulmonary
embolism or deep vein thrombosis).

- 13. Hypogonadal (T <175 ng/dL) or on continuous testosterone replacement therapy

- 14. Positive serology for HIV-1, HIV-2 or HTLV-1, HTLV-2

- 15. Active hepatitis B or C

- 16. Any medical intervention, any other condition, or any other circumstance which, in
the opinion of the investigator or the sponsor's Medical Monitor, could compromise
adherence with study requirements or otherwise compromise the study's objectives.