Table 2 Summary of AOC3 inhibitor preclinical and clinical findings in DR and DME
Agent | Preclinical findings | Clinical findings in DR | Other therapeutic areas of interest |
|---|---|---|---|
ASP8232 | Inhibited plasma VAP1 (AOC3) activity and improved retinal hyperpermeability and plasma total antioxidant status in rat DME model. More effective in reducing ocular hyperpermeability when combined with IVT anti-rat VEGF antibody than either agent alone [87] | VIDI study Phase 2a–CI-DME. Failed to reduce CST alone, no additional benefit in combination with ranibizumab [87] | Reduced residual albuminuria, a surrogate marker for disease progression, in patients with type 2 DM and CKD [88] |
RTU-1096 | Abrogated outer nuclear layer thickening and reduced upregulation of ICAM1 in mice after retinal laser photocoagulation [91] | Phase 1–healthy volunteers. Well tolerated at all tested doses [93] |  |
BI 1467335 (formerly PXS-4728A) | Inhibited neutrophil tethering and rolling, reduced inflammation in mouse models [89, 90] | ROBIN (NCT03238963) Phase 2a–NPDR. Primary safety endpoint met, unable to demonstrate a clear efficacy signal (development discontinued due to risk of DDI) [94, 95] | NCT03166735 Phase 2a–NASH. Results pending (development discontinued due to risk of DDI) [97, 98] |