NCX 470 is a novel nitric oxide (NO)-donating bimatoprost eye drop that leverages the potent intraocular pressure (IOP)-lowering effects of NO and prostaglandin analogs (PGAs). NCX 470 incorporates Nicox’s proprietary NO-donating research platform and bimatoprost in a single molecule. NCX 470 is designed to release bimatoprost and NO into the eye to lower IOP by two different pathways in patients with open-angle glaucoma or ocular hypertension. NO is a well-known small, naturally occurring signaling molecule that plays a key role in the regulation of IOP through activation of soluble guanylate cyclase (sGC). NO brings additional IOP-lowering efficacy by enhancing aqueous humor drainage from the eye via a different mechanism of action to that of PGAs. Bimatoprost, marketed under the brand name LUMIGAN® by AbbVie, Inc., is the leading branded PGA. PGAs are the most widely used class of drugs for IOP-lowering in patients with open-angle glaucoma or ocular hypertension. We believe that the proven dual mechanism of action can achieve superior IOP-lowering compared to the parent compound alone. Beneficial effects of NCX 470 have additionally been demonstrated in an in vivo model of retinal cell damage (see Press Release of September 29, 2021).
Topline results from the first Mont Blanc Phase 3 clinical trial evaluating the IOP lowering efficacy of once-daily dosed NCX 470 ophthalmic solution 0.1% compared to latanoprost ophthalmic solution 0.005% in patients with open-angle glaucoma or ocular hypertension were announced on October 31, 2022 (see also Press Release of November 19, 2024). The first of two Phase 3 trials for NCX 470, Mont Blanc, met the efficacy requirements for approval in the U.S. Daily dosing of NCX 470 0.1% met the primary efficacy objective of demonstrating non-inferiority to latanoprost 0.005%, with NCX 470 showing 8.0 to 9.7 mmHg IOP lowering from baseline. NCX 470 0.1% was statistically superior to latanoprost 0.005% in IOP reduction from baseline at 4 of the 6 timepoints, and numerically greater at all 6 timepoints. However, the secondary efficacy objective, statistical superiority to latanoprost, was not achieved. NCX 470 0.1% was well tolerated. Latanoprost, marketed as Xalatan and available as a generic, is the most prescribed PGA in the U.S.
The similarly designed and ongoing second Phase 3 trial, Denali, conducted at clinical sites in the U.S. and China is ongoing. The completion of recruitment of U.S. patients of Denali Phase 3 trial has been completed in July 2024. Topline results are expected in Q3 2025. The Denali trial also includes a long-term safety extension through 12 months.
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 U.S. and China.
Exploratory nonclinical studies in a well-defined model with optic nerve head and retina damage (ET-1-induced ischemia/reperfusion) investigated the NCX 470 effects beyond its IOP lowering properties. The results suggest that NCX 470 improves ocular perfusion and retinal function in damaged eyes compared to vehicle and to Lumigan® and may therefore have protective properties for the retina.
A Phase 3b clinical trial, Whistler, investigating NCX 470’s dual mechanism of action (NO and PGA) in IOP lowering has been initiated in December 2023. The Whistler trial will enroll approximately 20 healthy volunteers with ocular hypertension in a double-masked, placebo-controlled study which will investigate the action of NCX 470 on aqueous humor parameters including trabecular meshwork outflow and episcleral venous pressure. Each subject will participate in the trial for ~8 days. The results of Whistler trial are expected in Q1 2025.
Results from the Dolomites Phase 2 trial for NCX 470 in glaucoma were reported in 2019: (see Press Release of October 2, 2019).
NCX 470 is protected worldwide by composition of matter patents until 2029, with a potential extension of up to 5 years in the U.S. and EU and by formulation patents to 2039 in the U.S., EU, Japan and China as well other territories.