No significant cardiovascular disease . No contraindication for vaccinia immunization Concomitant Therapy . Subjects will be on concomitant androgen suppression therapy with a GnRH agonist or antagonist . Subjects may be on concomitant drugs to prevent bone loss or skeletal -related events, including bisphosphonates and denosumab . Subjects may receive palliative radiotherapy during the trial Excluded Therapy Chemotherapy: Concomitant use of chemotherapy is not allowed during the Treatment phase (approximately 5 months) of this trial. Concurrent immunotherapy or immunosuppressive therapy Anti-cancer radionuclides: Concomitant use of anti- cancer radionuclides is not allowed during the Treatment phase of this trial. Secondary hormonal therapies: Concomitant use of supplementary hormonal treatments is not allowed during the Treatment phase of this trial. Corticosteroids: Concomitant chronic use of systemic corticosteroids is not allowed during the Treatment phase of the study. The use of inhaled corticosteroids, nasal sprays, and topical creams for small body areas is allowed. Dose and Administration PROSTVAC -V/F is provided at the following doses based on the doses of PROSTVAC -V/F used in the randomized controlled Phase 2 trial of 122 men, TBC-PRO -002. • 2 x 108 Infectious Units ( Inf.U )/0.5 ml for vaccinia (PROSTVAC -V). • 1x 109 Inf.U/0.5 ml for fowlpox (PROSTVAC -F). • 1x 109 Inf.U/0.5 ml for placebo (empty fowlpox vector). PROSTVAC -V/F is administered by sc injection with the following schedule: • 1 PROSTVAC -V (or placebo) priming vaccination (Week 1) Protocol BNIT -PRV- 301; Amendment 7 PROSTVAC -V/F Version 2.7, 08 February 2017 CONFIDENTIAL AND RESTRICTED 15 Amend 7 Disclosure requires written consent from Bavarian Nordic , Inc. • 6 PROSTVAC -F (or placebo) booster vaccinations (Weeks 3, 5, and then 9, 13, 17, and 21) GM-CSF is provided at 100 μg per sc injection (on Days 1 – 4) for each vaccination. GM- CSF placebo is bacteriostatic saline for injection and is delivered on the same s chedule. Statistical Methods Statistical success with respect to the primary objective is defined as success for either of the following comparisons: • Superiority of Arm V+G over Arm P for all subjects randomized to these arms. • Superiority of Arm V over Arm P for all subjects randomized to these arms. The significance levels to be used for the analyses associated with these two comparisons will protect the overall study type I error probability to be one- sided 0.025 or less. The possibility of delayed va ccine effect is taken into account in computing the required number of deaths, (as modeled from the randomized Phase 2 trial). The projected trial size is 400 subjects per arm (approximately 1,200 subjects) with at least 85% power, and the final analyses will be event - driven and take place when 534 deaths have been realized for the comparisons involving all subjects randomized (Arm V+G versus Arm P, and separately Arm V versus Arm P). Protocol BNIT -PRV - 301; Amendment 7 PROSTVAC -V/F Version 2.7, 08 February 2017 CONFIDENTIAL AND RESTRICTED 16 Amend 7 Disclosure requires written consent from Bavarian Nordic , Inc. 1.0 BACKGROUND AND RATIO NALE 1.1 Rationale Bavarian Nordic, Inc . (BNI) previously known as BN ImmunoTherapeutics, Inc. (BNIT) is developing PROSTVAC -V/F for the treatment of prostate cancer (Madan 2009). The PROSTVAC vaccine product is comprised of two biologic agents, PROSTVAC -V and PROSTVAC -F. These are two different poxvirus vectors, recombinant vaccinia and fowlpox viruses, respectively, encoding the genes for prostate - specific antigen (PSA) with the L155 mutation in combination with a triad of human costimulatory molecules, B7.1, ICAM -1, and LFA -3 (TRICOM™; TRICOM) . They are used to introduce tumor -associated antigens (TAAs) and costimulatory molecules into patients with metastatic prostate cancer. The vaccinia and fowlpox viruses encoding PSA and TRICOM are used in a prime - boost vaccination regimen to optimize immu ne responses against prostate cancer tumor cells. The proposed treatment is a PSA -based immunization strategy. PROSTVAC -V/F is a viral vector -based product that is administered over seven subcutaneous vaccinations, over a five month period. It is intended to generate immune responses to prostate specific antigens and prostate cancer cells. It uses poxviral vectors to introduce modified PSA to the patient in an immunogenic manner to break self - tolerance and generate immune responses directed against prostate cancer cells. A double - blind randomized Phase 2 trial found longer survival for men randomized to receive PROSTVAC -V/F, where an overall median survival of 16.6 months was noted for control vector -treated subjects versus 25.1 months for PROSTVAC -V/F-treated subjects, hazard ratio 0.56 (95%CI 0.38 - 0.88), and p=0.006. PROSTVAC -V/F is an outcome of more than 15 years of poxvir al vector development and evaluation by the NCI, the former Therion Biologics Corporation (Therion), and BNI . Over 570 patients have been treated with related PSA -containing poxviral vectors, and over 300 patients have been treated with the current PROSTVA C- V/F regimen . A large database (see Investigator’s Brochure) exists from safety evaluations in animals and in humans for PROSTVAC -V/F. BNIT -PRV - 301 will evaluate the efficacy of PROSTVAC -V/F in men with asymptomatic or minimally symptomatic, metastatic ca stration -resistant prostate cancer (mCRPC). 1.2 Background 1.2.1 PROSTVAC -V/F Development Program Bavarian Nordic A/S (BN), , is the parent company of BNI, and is now the sole manufacturer of PROSTVAC -V/F. BN has manufactured poxviral - based products since 1995, ranging from bench - scale through commercial, and has the experience and technical expertise to culture the vaccine vectors, and to produce final frozen liquid formulations. The manufacturing technology and methodology originally devel oped at Therion have been transferred and further developed . Phase 3 clinical trial material will be manufactured . Protocol BNIT -PRV- 301; Amendment 7 PROSTVAC -V/F Version 2.7, 08 February 2017 CONFIDENTIAL AND RESTRICTED 17 Amend 7 Disclosure requires written consent from Bavarian Nordic , Inc. The plan for the continued clinical development of PROSTVAC -V/F in men with mCRPC is informed in particular by the Phase 2 study conducted under former BB -IND 10428. This study in metastatic disease demonstrated that (i) recombinant vaccinia and fowlpox viruses are well tolerated vectors for administration to subjects with prostate cancer, and (ii) prolonged survival is achieved in subjects treated with PROSTVAC -V/F versus subjects administered the control. The planned Phase 3 clinical program to be conducted by BNI will include one w ell-powered, randomized, placebo- controlled, double- blind, multi -center, multi -country trial designed to evaluate PROSTVAC -V/F with and without GM- CSF for the treatment of mCRPC. This trial will be conducted globally.