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There are clearly some patients who DO respond better to the combination therapy at some point in the treatment regime. As the trials progress and the number of treated patients increases the understanding of how the drug works and who benefits most will improve.

"Mean change in BCVA at week 12 compared to baseline was 5.9 letters for OPT-302 combination therapy
and was similar in the Eylea control group at 6.1 letters. 52% of patients in the OPT-302 combination
and 60% of patients in the Eylea control group gained ≥5 letters, however a higher proportion of patients
gained ≥10 and ≥15 letters of vision following OPT-302 combination treatment compared to Eylea control.
The proportion of patients gaining ≥10 letters from baseline to week 12 was 26.7% in the OPT-302
combination group and 22.5% in the Eylea control. In addition, 12% of patients in the OPT-302
combination group and 7.5% of patients in the Eylea control group had ≥15 letter gains respectively. The
percentage of patients who lost 5 or more letters was 2.7% in the OPT-302 combination therapy group,
and 5% in the Eylea control group.

An exploratory subgroup analysis was conducted in patients with a prior anti-VEGF-A treatment history
of only receiving previous Eylea to assess the effects of OPT-302 combination therapy following the most
optimal first-line standard of care used to achieve maximal VEGF-A inhibition. In this subgroup, the mean
change in BCVA at week 12 compared to baseline was 8.6 letters for OPT-302 + Eylea and 5.0 letters in
patients who continued on Eylea monotherapy. The proportion of patients in the subgroup gaining ≥10
and ≥15 letters from baseline to week 12 was 50% and 16.7% in the OPT-302 combination group
respectively and 0% for both parameters in the Eylea control. The percentage of patients losing 1 or
more letters from baseline to week 12 was 8.3% in the OPT-302 + Eylea group, and 12.5% for the Eylea
control.

Retinal thickness measured by CST on spectral domain optical coherence tomography (SD-OCT), was
reduced by -52.16 µm, from 436 µm at baseline to 384 µm at week 12 following OPT-302 combination
therapy. The mean CST was reduced by -34.92 µm, from 422 µm at baseline to 389 µm at week 12 in
the Eylea control group.

The proportion of patients with ≥ 1 step improvement in DRSS was 21.4% with OPT-302 combination
therapy and 17.5% in the Eylea control group. The proportion of patients who had a severity score of
between 47 and 53, representing moderately-severe to severe non-proliferative diabetic retinopathy
(NPDR), was 65.3% at baseline and 54.8% following OPT-302 combination therapy to week 12, whereas
there was no change in the Eylea monotherapy group with 60% of patients having moderately-severe to
severe NPDR at baseline and week 12.

These secondary analyses were conducted in all evaluable patients in the Per Protocol population.
Similar outcomes were also observed in the Intent to Treat Population."