Safety and Exploratory Efficacy Study of SF0166 for the Treatment of Diabetic Macular Edema (DME)

This is a prospective, randomized, double-masked, multicenter, Phase I/II clinical study in
which up to 40 eligible subjects with active Diabetic Macular Edema (DME) will be randomized
to 1 of 2 treatment arms in a 1:1 ratio as follows: SF0166 low dose twice daily (BID) or
SF0166 high dose BID.

The study population will include male and female subjects, aged 18 or older, with diabetic
macular edema (i.e., retinal thickening secondary to type 1 or type 2 diabetes mellitus with
Diabetic Macular Edema (DME) with central subfield thickness ≥325 microns (μm) on spectral
domain optical coherence tomography [OCT]) and no treatment with antivascular endothelial
growth factor (VEGF) therapy in the study eye within up to 60 days of study entry.

If a subject qualifies in both eyes, SF0166 may be administered to both eyes (study eye and
non-study eye) at the discretion of the Investigator.

Study subjects will administer the randomly assigned treatment for 28 days. There is an
additional 28-day post-treatment follow-up period. All study subjects will return for
examination every 2 weeks for 8 weeks (2 months).

All outcomes and assessments will be summarized descriptively for Days 0, 14, 28, 42, and
56. No formal hypotheses will be tested.

Inclusion Criteria:

1. Male or female, 18 years of age or older.

2. Retinal thickening secondary to type 1 or type 2 diabetes mellitus with Diabetic
Macular Edema (DME) defined as central subfield thickness ≥325 microns (µm) on
spectral domain OCT in the study eye.

3. Best-corrected Visual Acuity (BCVA) between 78 and 25 letters, inclusive, in the
study eye at the screening/randomization visit using Early Treatment Diabetic
Retinopathy Study (ETDRS) testing, with BCVA decrement primarily attributable to
Diabetic Macular Edema (DME).

4. Treatment naïve (i.e., no previous anti--vascular endothelial growth factor [VEGF]
treatment in the study eye) or previously treated study eye with adequate washout
defined below:

1. Lucentis (ranibizumab): 30-day washout

2. Avastin (bevacizumab): 30-day washout

3. Eylea (aflibercept): 60-day washout

4. Macugen (pegaptanib): 45-day washout

5. Willing and able to return for all study visits.

6. Able to adhere to the study dosing requirements.

7. Understands and signs the written informed consent form.

Exclusion Criteria:

1. Active proliferative diabetic retinopathy (PDR) in the study eye, such as
neovascularization of the optic disc (NVD), neovascularization elsewhere (NVE),
vitreous hemorrhage, or neovascular glaucoma.

2. Uncontrolled glaucoma or ocular hypertension in the study eye defined as an
intraocular pressure (IOP) >25 millimeter of mercury (mmHg) regardless of concomitant
treatment with IOP-lowering medications.

3. Uncontrolled hypertension defined as systolic >180 mmHg or >160 mmHg on 2 consecutive
measurements (during the same visit) or diastolic >100 mmHg on optimal medical
regimen.

4. Screening glycated hemoglobin (HbA1c) blood test >12.0%.

5. Previous panretinal photocoagulation (PRP) in the study eye within 4 months of study
enrollment, or the need for PRP during the study based on the Investigator's opinion.

6. Previous focal laser photocoagulation in the study eye, within the foveal avascular
zone.

7. Intravitreal/periocular/topical ocular steroids of any type in the study eye within
90 days (3 months) prior to study enrollment.

8. Placement of Iluvien or Retisert (fluocinolone acetonide intravitreal implant) in the
study eye within 36 months (3 years) prior to study enrollment.

9. Use of Ozurdex (dexamethasone intravitreal implant) in the study eye within 180 days
(6 months) prior to study enrollment.

10. Significant epiretinal membrane, posterior hyaloidal traction, and/or vitreomacular
traction in the study eye as determined by the optical coherence tomography (OCT)
results.

11. Previous pars plana vitrectomy in the study eye.

12. Any intraocular surgery in the study eye within 90 days (3 months) prior to study
enrollment.

13. Yttrium aluminium garnet (YAG) laser treatment in the study eye within 30 days (1
month) prior to study enrollment.

14. Concomitant use of any topical ophthalmic medications in the study eye, including dry
eye or glaucoma medications, unless on a stable dose for at least 90 days (3 months)
prior to study enrollment and expected to stay on stable dose throughout study
participation. Artificial tears are allowed.

15. High myopia in the study eye, with a spherical equivalent of >8.00 Diopters (D) at
screening.

16. Chronic or recurrent uveitis in the study eye.

17. Ongoing ocular infection or inflammation in either eye.

18. A history of cataract surgery complicated by vitreous loss in the study eye.

19. Congenital eye malformations in the study eye.

20. A history of penetrating ocular trauma in the study eye.

21. Mentally handicapped.

22. Females of childbearing potential (i.e., who are not postmenopausal for at least 1
year or surgically sterile for at least 6 weeks prior to Visit 1 -
Screening/Randomization) who are lactating, or who are pregnant as determined by a
positive urine pregnancy test (UPT) at Visit 1 - Screening/Randomization. Women of
childbearing potential must agree to use acceptable methods of birth control
throughout the study. Acceptable methods of birth control include tubal ligation,
transdermal patch, intrauterine devices/systems, oral/implantable/injectable or
contraceptives, sexual abstinence, double barrier method, or vasectomized partner.

23. Participation in any other investigational device or drug clinical research study
within 30 days of Visit 1 - Screening/Randomization.

24. Contraindication to the study medications or fluorescein dye.

25. Other ocular pathologies that in the Investigator's opinion would interfere with the
subject's vision in the study eye.