A Study to Evaluate Oral VT-464 in Patients With Castration-Resistant Prostate Cancer

This is a Phase 1/2 study of seviteronel in subjects with castration-resistant prostate
cancer (CRPC). Phase 1 was a dose-escalation study enrolling subjects with CRPC that were
either "treatment naïve" (not treated with previous abiraterone or enzalutamide), or treated
with one or more of the following: abiraterone, enzalutamide, or chemotherapy.

Phase 2 is an open-label, multi-center cohort-expansion study to further determine the
efficacy and safety of seviteronel in two CRPC populations with documented rising PSA with or
without bone or soft tissue disease progression during treatment with: abiraterone or
enzalutamide for ≥ 12 weeks (Group 1) abiraterone and enzalutamide; treatment should be ≥ 12
weeks for at least one agent (Group 2)

Inclusion Criteria:

1.18 years of age or older 2. Able to provide written informed consent or have their legal
representatives provide written informed consent 3. Documented histological or cytological
evidence of adenocarcinoma of the prostate. Subjects whose pathology reports are no longer
available may be enrolled if, in the opinion of the investigator, the subject has a
clinical course consistent with prostatic adenocarcinoma 4. ECOG Performance Status of 0 or
1 5. Undergone orchiectomy, or have ongoing LHRH analogue therapy prior to C1D1. Subjects
on LHRH analogues should remain on these agents for the duration of the study 6. Castrate
levels of testosterone less than or equal to 50 ng/dl (or 1.7 nmol/L) and have progressive
disease at Screening defined as PSA rise determined by a minimum of 2 rising PSA values
greater than or equal to 1 week between each assessment. The PSA value at the Screening
visit must be greater than or equal 2ng/mL with or without: Soft tissue disease progression
defined by RECIST 1.1 at Screening or less than or equal to 28 days of C1D1. Measurable
disease is not required for entry.

Lymph nodes greater than or equal to 1.5cm (short axis) are considered measurable disease
bone disease progression defined by greater than or equal 2 new lesions on bone scan at
Screening, or less than or equal 28 days of C1D1 7. Have received abiraterone and/or
enzalutamide. Subject must have received either abiraterone or enzalutamide for greater
than or equal to 12 weeks. Other second generation CYP17 inhibitors/androgen receptor
antagonists including but not limited to TAK-700 (orteronel), TOK-001 (galeterone) may have
been taken in place of abiraterone and ARN-509 (apalutamide) may have been taken in place
of enzalutamide.

8. Adequate hematopoietic function as evidenced by:

- WBC greater than or equal to 3,000/μl

- ANC greater than or equal to 1,500/μl

- Platelet count greater than or equal to 100,000/μl

- HGB greater than or equal to 10 g/dl and not transfusion dependent 9. Adequate liver
function, including all the following:

- Total serum bilirubin less than or equal to 2.0 x ULN unless the subject has
documented Gilbert syndrome;

- Aspartate and alanine aminotransferase (AST & ALT) less than or equal to 3.0 x ULN or
less than or equal to 5.0 x ULN if subject has liver metastasis;

- Alkaline phosphatase less than or equal to 3.0 x ULN or less than or equal to 5 x ULN
in case of bone metastasis and/or hepatic metastasis 10. Subjects must have adequate
renal function as evidenced by a serum creatinine of less than or equal to 2.0 mg/dl
11. Potassium (K+) greater than or equal to 3.5 mEq/l 12. Subject and his female
partner who is of childbearing potential must use 2 acceptable methods of birth
control (one of which must include a condom as a barrier method of contraception)
starting at Screening and continuing throughout the study period and for 3 months
after final study drug administration.

- Two acceptable forms of birth control include:

1. Condom (barrier method of contraception), and

2. One of the following:

1. Oral, injected or implanted hormonal contraception

2. Placement of an intrauterine device (IUD) or intrauterine system (ISU)

3. Additional barrier methods of contraception: Occlusive cap (diaphragm or
cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.

4. Vasectomy or surgical castration greater than or equal to 6 months prior to
Screening.

13. Able to swallow study medication 14. Able to comply with study requirements

Exclusion Criteria

Each subject eligible to participate in this study must not have any of the following:

1. Received sipuleucel-T (Provenge ®) treatment within 28 days of C1D1

2. Received 5-alpha reductase inhibitors such as finasteride (PROSCAR®, PROPECIA®), or
dutasteride (AVODART®) within 28 days of C1D1

3. Received any investigational agent less than or equal to 28 days of C1D1

4. Received palliative radiotherapy less than or equal to 2 weeks of C1D1

5. Symptomatic CNS metastases

6. History of another invasive malignancy less than or equal to 3 years of C1D1

7. A QTcF interval of greater than 470 msec; if the Screening ECG QTcF interval is
greater than 470 msec, it may be repeated, and if repeat less than or equal to 470
msec, the subject may be enrolled

8. Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia, ventricular
fibrillation, torsades de pointes, second degree or third degree atrioventricular
heart block without a permanent pacemaker in place)

9. Started a bone modifying agent (e.g. bisphosphonates, denosumab) less than or equal to
28 days of C1D1 (note: ongoing bone modifying agents administered less than 28 days
are allowed)

10. Any medical condition that could preclude subject participation in the study, pose an
undue medical hazard, or which could interfere with study results

11. Class III or IV Congestive Heart Failure (CHF) as defined by the New York Heart
Association (NYHA) functional classification system within the previous 6 months

12. A history of loss of consciousness or transient ischemic attack less than or equal to
12 months of C1D1

13. Known active HIV, Hepatitis B, or Hepatitis C infections

14. Known or suspected hypersensitivity to seviteronel, or any components of the
formulation

15. Any other condition which in the opinion of the investigator would preclude
participation in the study