A Phase 1, Multicenter, Open-Label, Dose Escalation and Expansion Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of Orally Administered FHD-286 in Subjects with Metastatic Uveal Melanoma

This Phase 1, multicenter, open-label, dose escalation and expansion study is designed to
assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and
preliminary clinical activity of FHD-286 oral monotherapy in subjects with metastatic Uveal
Melanoma (UM).

Key Inclusion Criteria:

- Male or female subjects ≥ 18 years of age

- Subject must have a diagnosis of metastatic histologically or cytologically confirmed
UM. If histologic or cytologic confirmation of the primary tumor is not available,
clinical confirmation of a diagnosis of metastatic UM, as per standard practice for
UM, by the treating investigator can be obtained, and fall into any of the following
categories:

1. Newly diagnosed subject who has not yet received liver-directed or systemic
treatment

2. Subjects ineligible for any available therapy likely to convey clinical benefit

3. Subjects who have disease progression after treatment with available therapies
and/or who is intolerant to those treatments.

- Subject must have measurable disease by RECIST v1.1, defined as at least 1 lesion that
can be accurately measured in at least 1 dimension (longest diameter to be recorded)
as ≥ 10 mm with calipers and/or CT scan. Measurable lesions cannot have undergone any
local treatment (including liver-directed radio- or immune-therapies) or radiation,
unless there has been interim progression of that lesion, nor can any local treatment
or radiation involving measurable lesions be anticipated.

Note: A malignant lymph node must be ≥ 15 mm on the short axis when assessed by CT scan to
be considered pathologically enlarged and measurable.

- Willingness to provide newly obtained tumor tissue at baseline and on treatment unless
contraindicated by medical risk in the opinion of the treating physician

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤ 2. a.) Arm 2
(Dose Expansion Phase): Subjects enrolling in Arm 2 must have an ECOG PS of ≤ 3.

Key Exclusion Criteria:

- Subjects who have other malignancy which may interfere with the diagnosis and/or
treatment of metastatic UM.

- Subject has thrombocytopenia (platelets < 50 × 109/L) or another major bleeding
disorder/diathesis.

Note: Subjects with platelets < 50 × 109/L may be permitted to enroll only in Arm 2 of the
Dose Expansion Phase at the discretion of the Investigator and the Sponsor.

- Subject has active brain metastases and/or leptomeningeal disease. Subjects with known
CNS metastases are only permitted under the following conditions; exceptions may be
made on a case-by-case basis with the approval of the Sponsor: Brain metastases must
have been stable for approximately 2 months since completion of most recent
CNS-directed intervention. Subject may be on corticosteroids so long as the dose is
stable for approximately 14 days or decreasing at the time of study entry.
Anti-epileptic therapy is allowed so long as medications are not otherwise excluded
and seizures have been controlled for approximately 4 weeks since last anti-epileptic
medication adjustment.

1. Dose Escalation Phase: Subjects with known CNS metastases that meet the above
conditions are permitted to enroll in dose escalation.

2. Arm 1 (Dose Expansion Phase): Subjects with known or suspected CNS metastases are
excluded from Arm 1.

3. Arm 2 (Dose Expansion Phase): Subjects with CNS metastases that meet the above
conditions are permitted to enroll in Arm 2.

- Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infections; subjects with a
sustained viral response to HCV treatment or immunity to prior HBV infection will be
permitted. Subject has known positive HIV antibody results or acquired
immunodeficiency syndrome (AIDS)-related illness; subjects with CD4+ T-cell counts
greater than or equal to 350 cells/µL will be permitted, as will subjects who have not
had an AIDS-related illness within the past 12 months

- Subjects with an active infection cannot be enrolled until any required antibiotic
and/or antifungal therapy has been completed and/or infection is determined to be
controlled

- Subjects who have an uncontrolled intercurrent illness.

- Known and possible risk for QT prolongation.

- Subject is on medications that are strong CYP3A inhibitors, are strong CYP3A inducers,
or are sensitive CYP3A substrates with narrow TIs

- Subject is on medications with narrow TIs that are sensitive P-gp or BCRP substrates
and are administered orally such as digoxin

- Subjects who require clinically significant or increasing doses of systemic steroid
therapy or any other systemic immunosuppressive medication. The use of a stable dose
of systemic steroids and/or immunosuppressive medication is permitted with Sponsor
approval. Local or targeted steroid and immunosuppressive therapies (e.g. inhaled or
topical steroids) are acceptable. Appropriate steroid replacement to manage endocrine
toxicities resulting from prior systemic anticancer therapy is permitted. See
exclusion criterion 3 for exceptions regarding steroid therapy for subjects with CNS
metastases. See exclusion criterion 13 for exclusions regarding medications that are
strong CYP3A inhibitors, strong CYP3A inducers, or sensitive CYP3A substrates with
narrow TIs.

- Subjects have undergone any prior treatment with a BRG1/BRM inhibitor.