Nicox SA announced future development and partnering plans for NCX 470, a novel nitric oxide (NO)-donating bimatoprost eye drop, currently in Phase 3 development for the lowering of intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. The program of studies is planned to include evaluation of the effect of NCX 470 on ocular perfusion pressure through Episcleral Venous Pressure (EVP) and Optical Coherence Tomography (OCT) measurements of retinal vessels in which NCX 470's ability to lower episcleral venous pressure as well as enhance outflow through the trabecular meshwork will be evaluated. Additionally, retinal blood vessel density will be studied in a separate clinical trial using OCT-angiography to fully understand effects on retinal blood flow. Together, these studies are designed to validate NCX 470's dual mechanism of action in humans and potentially demonstrate some of the beneficial effects on the retina that have been observed in nonclinical models. The planned initiation of these clinical studies is included in the Company's cash runway to mid-November, 2023,
however the studies are not expected to be completed by that date and will require additional funding. Elevated IOP is the main risk factor in glaucoma; however, a variety of IOP-independent risk factors, including ischemia (inadequate blood supply), contribute to damage of the optic nerve head and the retina, ultimately causing vision loss. NO is a potent vasodilator, and Nicox has previously demonstrated1 a partial reversal of the ischemic effects on ocular hemodynamics and retinal dysfunction by administering a Nicox NO-donating compound. NCX 470 is a novel, nitric oxide (NO)-donating bimatoprost eye drop that leverages the potent 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 pathways in patien ts 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 than that engaged by prostaglandin analogs. 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.
NCX 470 is currently in Phase 3 development for the lowering of intraocular pressure in patients with open-angle glaucoma or elevated intraocular pressure. The program consists of two trials, Mont Blanc and Denali. Topline results from the Mont Blanc trial were reported on October 31, 2022. The similarly designed, ongoing, second Phase 3 trial, Denali, is being conducted at clinical sites in the U.S. and China, with topline results expected after 2024. The Denali trial also includes a long term safety extension through to 12 months, and is being jointly conducted and equally financed with Chinese partner, Ocumension Therapeutics. The Mont Blanc and Denali trials have been designed to fulfill the regulatory requirements to support New Drug Application (NDA) submissions in the U.S. and China and will also provide data for other countries accepting the same clinical data package for approval. The design of the efficacy part of the Denali trial is identical to that of Mont Blanc, however there is no guarantee that the results will be the same. Both trials are necessary, and certain additional clinical and nonclinical data will also be required, to complete NDA submissions in both the U.S. and China. Should NCX 470 be developed for other territories, for example Europe or Japan, there may be additional requirements.