Study of Brimonidine Tartrate Nanoemulsion Eye Drops in Patients With Ocular Graft-vs-Host Disease

Ocular GVHD (oGVHD) is a common complication that occurs in 40-60% of patients who have
undergone allogeneic bone marrow transplants. Driven by inflammation, oGVHD can result in
damage to the ocular surface and tear-producing glands, which over time significantly
diminishes quality of life and restricts daily activities due to visual impairment.

Early studies in animals and humans indicate that Brimonidine nano-emulsion, also known as
OCU300, may relieve the signs and symptoms of oGVHD. These symptoms include blurry vision,
foreign body sensation, burning sensation, severe light sensitivity, chronic conjunctivitis
(pink or red eye), dry eyes and eye pain.

This study will be a randomized, placebo-controlled, double-masked, multicenter phase 3 study
in the United States conducted at approximately 15 centers. Upon meeting the eligibility
criteria, enrolled subjects with a diagnosis of definite oGVHD will be randomly assigned in a
2:1 (test: control) fashion to receive either Brimonidine Nanoemulsion Eye Drops 0.18%
investigational product (test) or ophthalmic buffered saline (placebo).

Inclusion Criteria:

- Men or women ≥ 18 years of age

- Diagnosis of definite oGVHD using the International Chronic Ocular GVHD Consensus
Group Revised Diagnostic criteria in at least one eye.

- Ocular Discomfort score ≥ 3

- Validated Bulbar Redness score ≥ 40 in both eyes

- Subjects who are capable and willing to provide informed consent and follow study
instructions

- Intraocular pressure (IOP) ≥ 5 mmHg and ≤22 mmHg in each eye

- Women who are not pregnant or lactating or post-menopausal or have undergone a
sterilization procedure

Exclusion Criteria:

- Allergic to brimonidine or any similar products, or excipients of brimonidine

- Currently receiving any brimonidine or other treatment for glaucoma

- Receiving or have received any investigational drug or device within 30 days of
screening

- Current use of contact lenses 14 days prior to screening

- Active ocular infection or ocular allergies

- Any history of eyelid surgery or ocular surgery within the past 3 months

- Corneal epithelial defect larger than 1 mm (squared) in either eye

- Received corticosteroid-containing eye drops within 14 days prior to screening or
planned use during the study

- Any change in corticosteroid-containing eye drops, systemic
corticosteroids/immunosuppressives, topical ocular antibiotics, cyclosporine
ophthalmic emulsion 0.05% (Restasis®), cyclosporine ophthalmic solution 0.09% (Cequa®)
or lifitegrast ophthalmic solution 5% (Xiidra®), or autologous serum tears within 30
days prior to screening or planned change during the study