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. The first of two Phase 3 trials for NCX 470, Mont Blanc, met the efficacy requirements for approval in the United States. 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 intraocular pressure lowering from baseline. NCX 470 0.1% was statistically superior to latanoprost 0.005% in intraocular pressure 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 and topline results are expected in 2025. The Denali trial also includes a long-term safety extension through 12 months.
Mont Blanc and Denali 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 IOP lowering. 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, the Whistler trial, investigating NCX 470’s dual mechanism of action (NO and prostaglandin analog) in IOP lowering is planned to start in H2 2023. Another Phase 3b clinical trial exploring the potential benefits of NCX 470 on the retina is expected to start in 2024. The Whistler trial will evaluate the effect of NCX 470 on Episcleral Venous Pressure (EVP) and outflow through the trabecular meshwork. The other Phase 3b trial will evaluate ocular perfusion via Optical Coherence Tomography (OCT) angiography on retinal vessels. Together, these trials are designed to validate NCX 470 dual mechanism of action in humans and potentially demonstrate some of the beneficial effects of NCX 470 on the retina that have been observed in nonclinical models.
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