Study to Evaluate Effects of Emixustat Hydrochloride in Subjects With Proliferative Diabetic Retinopathy

This is a multicenter, randomized, double-masked, placebo-controlled study to evaluate the
effects of emixustat in subjects with PDR. Subjects will be randomly assigned to either
emixustat or placebo arms and treated once daily (QD) for 12 weeks. Doses of emixustat will
be doubled on a weekly basis until week 4 after which all subjects will be held at a stable
dose for the remainder of the 12-week dosing regimen. Subjects in the placebo group will be
mock-titrated on the same schedule as those in the emixustat arm.

Inclusion Criteria:

- Able and willing to provide written informed consent

- Documented diagnosis of type 1 or type 2 diabetes mellitus

- Meets specific ocular criteria for the study eye including but not limited to, the
presence of PDR with or without diabetic macular edema in study eye for which
treatment can be deferred for at least 4 weeks after Day 1 visit

- Media clarity, pupillary dilation, and subject cooperation sufficient to obtain
adequate assessments

Exclusion Criteria:

- Any condition that would preclude participation in the study (e.g., unstable medical
status including blood pressure, cardiovascular disease or glycemic control)

- History of myocardial infarction or other acute cardiac event

- History of chronic renal failure requiring dialysis or kidney transplant

- Prior participation in any clinical study of emixustat

- Treatment with any investigational study drug within 30 days of screening

- Known allergy to fluorescein sodium for injection in angiography

- Treatment with specific prohibited medications or therapy beginning 4 weeks prior to
screening and throughout the duration of the study

- History of systemic anti-VEGF or pro-VEGF treatment within 4 months prior to
randomization

- Pre-specified laboratory abnormalities at screening

- Specific ocular characteristics in the study eye

- Male subjects who are not surgically sterile and are not willing to practice a
medically accepted method of birth control with their female partner of childbearing
potential from screening through 30 days following completion of the study

- Female subjects of childbearing potential who are not willing to practice a medically
accepted method of birth control with their non-surgically sterile male sexual partner
from screening through 30 days following completion of the study

- Female subjects who are pregnant or lactating