0 20 40 60 0 50 100 150 Hours % Resistance No Exposure VEGF + IL-6/R VEGF + IL-6/R + anti-VEGF VEGF + IL-6/R + KSI-101 VEGF + IL-6/R + anti-IL-6 Bispecific KSI-101 restores barrier resistance from pre-existing insult greater than anti-IL-6 or anti-VEGF monotherapies alone Exposure Start (Exogenous VEGF and IL-6) Treatment High barrier resistance Intact tight junctions KSI-101 restores barrier integrity to no exposure levels Anti-VEGF and anti-IL- 6 monotherapy only partially restore barrier function No Exposure VEGF + IL-6/R + KSI-101 VEGF + IL-6/R + anti-VEGF VEGF + IL-6/R + anti-IL-6 VEGF + IL-6/R HUVEC cells were treated as indicated after growth to establish barrier 4 VEGF + IL6 disrupt the barrier integrity synergistically Preclinical model of endothelial cells simulating the blood-retinal barrier