A Phase 1 Study of FOR46 in Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC)

This study is designed to evaluate the safety, tolerability and antitumor activity of FOR46
in patients with metastatic castration-resistant prostate cancer. This study will be
conducted in two parts:

Dose escalation:

This part will evaluate increasing doses of FOR46 to identify the maximum tolerated dose
(MTD). The first patient enrolled on the study will receive the lowest dose of FOR46. Once
this dose is shown to be safe, a second patient will be enrolled at the next higher dose.
Patients will continue to be enrolled into either single or multiple patient groups receiving
increasing doses until the MTD is reached.

Dose expansion:

This part of the study will further evaluate the safety, tolerability and antitumor activity
of FOR46 at a dose shown to be safe in the dose escalation part of the study. Patients will
be enrolled into 1 of 2 groups, based on histology.

Inclusion Criteria:

- Male ≥ 18 years of age

- Has histologically confirmed prostate cancer that is metastatic and has progressed as
defined by PCWG3 criteria during or after treatment with at least 1 ASI (eg,
abiraterone, enzalutamide, apalutamide), or another second-generation anti-androgen or
cytochrome P450 (CYP)17A1 inhibitor, with the most recent ASI administered in the
castration-resistant setting

- Has serum testosterone levels < 50 ng/dL during screening. Patients without a history
of bilateral orchiectomy are required to remain on luteinizing hormone-releasing
hormone (LHRH) analog during the course of protocol therapy

- ECOG performance status of 0 or 1

- Adequate hematologic, renal and hepatic function

- Males with female partners of childbearing potential must agree to use 2 effective
methods of contraception

- Patients must provide signed informed consent

- Patients enrolled into the dose expansion phase must be willing to undergo a
metastatic tumor biopsy or has tissue available from a prior post-castration resistant
tumor biopsy

Exclusion Criteria:

- Persistent clinically significant toxicities from previous anticancer therapy

- Prior treatment with cytotoxic chemotherapy for mCRPC (chemotherapy in the
hormone-sensitive setting is allowed if > 6 months before study entry)

- Has received external-beam radiation or systemic anticancer therapy within 14 days
before first dose of FOR46

- Has received treatment with an investigational drug within 28 days before first dose
of FOR46

- Clinically significant cardiovascular disease

- Uncontrolled, clinically significant pulmonary disease

- Uncontrolled intercurrent illness

- Requires medications that are strong inhibitors or strong inducers of CYP3A4