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Table 2 Summary of AOC3 inhibitor preclinical and clinical findings in DR and DME

From: Amine oxidase copper-containing 3 (AOC3) inhibition: a potential novel target for the management of diabetic retinopathy

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]
  1. CI-DME center-involving diabetic macular edema, CKD chronic kidney disease, CST central subfield thickness, DDI drug–drug interaction, DM diabetes mellitus, DME diabetic macular edema, ICAM1 intracellular adhesion molecule 1, IVT intravitreal, NASH non-alcoholic steatohepatitis, NPDR non-proliferative diabetic retinopathy; ROBIN Randomized, double-masked, placebo-controlled exploratory study to evaluate safety, tolerability, pharmacodynamics and pharmacokinetics of Orally administered BI 1467335 for 12 weeks with a 12 week follow up period in patients with Non-proliferative diabetic retinopathy without center-involved diabetic macular edema, VAP1 vascular adhesion protein 1, VIDI VAP1 inhibition in diabetic macular edema