Phase 2 Randomized Clinical Trial of Luminate® as Compared to Avastin® in the Treatment of Diabetic Macular Edema

To evaluate the safety and efficacy of Luminate® (ALG-1001) as compared to Avastin® in
patients with diabetic macular edema

- Stage 1: 120 eligible subjects with DME will be enrolled and randomized to one of 4
treatment groups at an allocation ratio of 1:1:1:1, i.e., one of three doses (1.0 mg, 2.0 mg
and 3.0 mg) of Luminate intravitreal injection or Avastin intravitreal injection. Subjects
will be followed monthly for 24 weeks (6 months).

Stage 2 (select sites): 75 eligible subjects with DME will be enrolled and randomized to one
of 5 treatment groups at an allocation ratio of 1:1:1:1:1; i.e., one of 2 doses of Luminate
intravitreal injection or Avastin intravitreal injection (0.5 mg and 1.0 mg). Subjects will
be followed monthly for 20 weeks (5 months).

Inclusion Criteria:

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

- Study eye with clinically significant diabetic macular edema (DME) with central
subfield thickness ≥ 350µm on spectral domain OCT

- Best corrected visual acuity (BCVA) of 20/50 to 20/320 ETDRS equivalent (65 letters to
23 letters) in the study eye, with BCVA decrement primarily attributable to DME.

- Treatment naïve, i.e., no previous anti-VEGF treatment in the study eye or no
anti-VEGF treatment in the 45 days prior to study enrollment.

- In the investigator's opinion, the subject still has significant intraretinal fluid
with room for improvement in both macular edema and BCVA.

- Intra-Ocular Pressure (IOP) is under control (i.e., IOP

≤ 25 mm in the study eye) and study eye is not receiving any IOP lowering drops.

- Willing and able to return for all study visits.

- Able to meet the extensive post-op evaluation regimen.

- Understands and signs the informed consent form.

Exclusion Criteria:

- Active proliferative diabetic retinopathy (PDR) in the study eye such as NVE, NVD,
vitreous hemorrhage, or neovascular glaucoma.

- Uncontrolled hypertension defined as systolic >180 mmHg or > 160 mmHg on 2 consecutive
measurements or diastolic > 100 mmHg on optimal medical regimen

- Screening HgA1c blood test > 10.0

- Focal laser photocoagulation or intravitreal/periocular steroids of any type in the
study eye within the last 90 days prior to study enrollment.

- A history of intravitreal anti-VEGF injection of any type in the study eye within the
last 45 days prior to study enrollment.

- History of rhegmatogenous retinal detachment, retinal tear(s), or traction retinal
detachments in the study eye.

- Epiretinal membrane and/or vitreomacular traction in the study eye as determined by
the central reading center.

- Previous pars plana vitrectomy in the study eye

- Any intraocular surgery in the study eye within the last 90 days prior to study
enrollment.

- YAG laser treatment in the study eye in last 30 days prior to study enrollment.

- High myopia in the study eye, with a spherical equivalent of >8.00D at screening

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

- Chronic or recurrent uveitis.

- Ongoing ocular infection or inflammation in either eye.

- A history of cataract surgery complications/vitreous loss in the study eye.

- Congenital eye malformations in the study eye.

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

- Mentally handicapped.

- Pregnant female, as determined for women less than 60 years old by a positive urine
pregnancy test during the screening window.

- Nursing female.

- Currently participating in any other clinical research study.

- Contraindication to the study medication.