Nicox Sa · EURONEXT:ALCOX
Nicox Sa — ARVO 2023
10 slides from Nicox Sa's conference presentation, April 2023
Slide 1: NCX 1728 enhances ocular perfusion and improves photoreceptor function in rabbits
NCX 1728, a nitric oxide (NO)-donating PDE-5 inhibitor, but not its des- nitro derivative (NCX 1880), enhances ocular perfusion and improves photoreceptor function in rabbits with endothelin-1 (ET-1)-induced ischemia/reperfusion injury of optic nerve head and retina Dr. Corinna Galli Senior Scientis
Slide 2: Background
Background Nitric oxide (NO)/soluble guanylyl cyclase (sGC) signaling in the eye: relevance to retinopathies Ischemia/reperfusion contributes to optic nerve head and the retina degeneration in many ocular conditions1 Nitric oxide (NO)/soluble guanylyl cyclase (sGC) plays a pivotal role in ocular
Slide 3: Nitric oxide (NO)/soluble guanylyl cyclase (sGC) signaling pathway
Nitric oxide (NO)/soluble guanylyl cyclase (sGC) signaling pathway Cellular/molecular mechanism/s Nitric oxide (NO) PDE5 sGC 5’-GMP cGMP GTP PKG [Ca2+]i IOP reduction (TM/SC-mediated) GTP: guanosine triphosphate Vasodilation sGC: soluble Guanylate Cyclase cGMP: cyclic guanosine monophosphate Muscle
Slide 4: NCX 1728 chemical structure & physicochemical properties
NCX 1728 (NO-donating avanafil) and NCX 1880 (des-nitro derivative of NCX 1728) Chemical structure & physicochemical properties Linker O Nitric oxide + N – O Avanafil N O O N N O Cl NH OH H3 C N N O O NH O N N N O Cl NH H3 C N NCX 1728 O O NH N (NO-donating avanafil) MW=643.09 NCX 1880 cLogD (pH 6.7
Slide 5: Aim of the study
Aim of the study Explore NCX 1728-mediated effects on ocular hemodynamics and retinal cell physiology in a rabbit model of ischemia/reperfusion injury of the optic nerve head and retina 5 ARVO 2023; April 23 – 27 | New Orleans, LA, USA – Session # 331, Presentation # 2823
Slide 6: ET-1-induced ischemia/reperfusion injury model: design & treatment schedule
Endothelin-1 (ET-1)-induced ischemia/reperfusion injury of optic nerve head (ONH) & retina in New Zealand White rabbits1 Design & treatment schedule ET-1 sub-tenon injection (250nM, 200µL, twice/week) Tenon’s capsule Conjuntiva Vehicle, NCX 1728 or NCX 1880 (des-nitro derivative) Sub-Tenon’s space (
Slide 7: ET-1-induced hemodynamic changes following ischemia/reperfusion injury
ET-1-induced hemodynamic changes following ischemia/reperfusion injury of optic nerve head (ONH) & retina in rabbits NCX 1728 (NO-avanafil) vs. NCX 1880 (respective des-nitro derivative) – head-to-head study O p h th a lm ic A rte ry R e s is tiv e In d e x V e h ic le , n = 8 REPRESENTATIVE ECOCOLO
Slide 8: ET-1-induced ERG changes following ischemia/reperfusion injury
ET-1-induced ERG changes following ischemia/reperfusion injury of optic nerve head (ONH) & retina in rabbits NCX 1728 (NO-avanafil) vs. NCX 1880 (respective des-nitro derivative) – head-to-head study L ig h t a d a p te d p h o to p ic r e s p o n s e 3 .0 ( c o n e r e s p o n s e ) V e h ic le , n
Slide 9: Concluding remarks
Concluding remarks NCX 1728 is a new molecular entity bearing two pharmacologically active moieties: NO and the PDE5-inhibitor Avanafil NCX 1728 reduces Ophthalmic Artery Resistive Index (OA-RI) following ET-1- induced ischemia/reperfusion injury NCX 1728 improves retinal cells activity and lo
Slide 10: Acknowledgement
Acknowledgement • Francesco Impagnatiello Nicox Research Institute, • Elena Bastia Bresso, Milan, Italy • Corinna Galli & Nicox Ophthalmics • Stefania Brambilla Durham, NC, USA • Douglas A. Hubatsch https://www.nicox.com • Emanuela Masini Dept. of Neuroscience, Psychology, Drug • Laura Lucarini Rese