New Data on Two Nicox’s Assets, NCX 470 and NCX 1728, Presented at ARVO 2023

Nicox announced that studies highlighting nonclinical data on NCX 470 and NCX 1728 have been presented at the Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting 2023 being held April 23-27, 2023 in New Orleans.

Poster title: NCX 470, a nitric oxide (NO)-donating bimatoprost, preserves rabbit eyes from biochemical and functional changes associated with endothelin-1 (ET-1)-induced ischemia/reperfusion injury of optic nerve head and retina.

Retina and optic nerve head vascular dysfunction in glaucoma is an important therapeutic target. Effectively managing the ocular blood flow may slow the progressive worsening of retinal cell function seen in glaucoma patients. This work shows compelling new evidence of retinal cell protective activity with NCX 470 in addition to its IOP lowering ability. Specifically, NCX 470 is found to reverse both hemodynamic and retinal cell impairments consequent to ET-1 induced ischemia/reperfusion injury in rabbits.

NCX 470, a novel NO-donating bimatoprost eye drop, is currently in phase 3 clinical development for the lowering of IOP in patients with open-angle glaucoma or ocular hypertension. Mont Blanc, the first of the two phase 3 clinical trials, has been completed and the results announced in October 2022. The second phase 3 clinical trial, Denali, is currently ongoing, and the results are expected in 2025. Mont Blanc and Denali trials have been designed to fulfill the regulatory requirements for safety and efficacy phase 3 trials to support NDA submissions in the US and China. Two new phase 3b clinical trials to evaluate the dual mechanism of action (NO and prostaglandin analog) in IOP lowering and the potential retinal benefits of NCX 470 are planned to start in H1 2023.

Paper presentation title: NCX 1728, a nitric oxide (NO)-donating phosphodiesterase type-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.

Nitric oxide has a well-established role in ocular blood flow and visual function. This work shows for the first time that our NO-donating avanafil derivative, NCX 1728, abolishes ET-1 induced retinal and vascular dysfunction in rabbits. Data point to nitric oxide/soluble guanylyl cyclase signaling pathway stimulation as the main contributor for these effects. NCX 1728 holds promise for the treatment of retinopathies where dysfunctional ocular perfusion and neovascularization are key pathophysiological features in disease progression.

NCX 1728 is an NO-donating phosphodiesterase-5 (PDE5) inhibitor, the lead compound of a new class of NO-donating molecules based entirely on NO-mediated activity. NCX 1728 is currently under preclinical evaluation for development in retinal conditions.