Abstract:Ojai visual biologyOT-301 (NCX 470), a new drug in the product pipeline, has been approved by the State Drug Administration (NMPA) to conduct a phase Ⅲ clinical trial in China to reduce intraocular pressure in patients with open-angle glaucoma or ocular hypertension. This is the third pipeline product to enter the Ⅲ phase in China, and it is also a potential "best-in-class" new drug for lowering intraocular pressure in glaucoma.

1477.HK announced on Oct. 23 that OT-301 (NCX 470), a new drug in the company's product line, has been approved by the State Drug Administration (NMPA) to conduct a phase Ⅲ clinical trial in China to reduce intraocular pressure in patients with open-angle glaucoma or ocular hypertension. This is the third pipeline product to enter the Ⅲ phase in China, and it is also a potential "best-in-class" new drug for lowering intraocular pressure in glaucoma.

According to reports, characterized by elevated intraocular pressure, visual field defect, optic nerve atrophy, there are about 60 million patients worldwide, of which about 7 million are blind. With the rapid popularization of electronic products, the prevalence of glaucoma is on the rise, and it is estimated that the number of glaucoma patients will exceed 100 million by 2040.

At present, glaucoma is mainly divided into primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG). The epidemiological risk factors of open-angle glaucoma are very complex. Chronic diseases such as intraocular pressure, age, family history and hypertension and diabetes may be the predisposing factors. In addition, open-angle glaucoma has few symptoms, so the clinical diagnosis is poor and is usually found accidentally during a comprehensive ophthalmology examination or at a later stage where the risk of irreversible vision loss is high. It can be predicted that there is still a lot of room for diagnosis and treatment in the open-angle glaucoma market, and the rapid increase in the number of patients with superimposed glaucoma brings a lot of imagination to the long-term drug demand of patients with superimposed glaucoma.

Drugs, laser and surgery are the three main treatment schemes for glaucoma treatment. these three treatments complement each other to achieve the ultimate goal of glaucoma treatment, that is, to preserve the existing visual function, stabilize the optic nerve and reduce visual field damage as much as possible. maintain patients' quality of life.

Drug reduction of intraocular pressure (IOP), as the most commonly used and preferred treatment, is widely used in patients with ocular hypertension and primary open-angle glaucoma. Among them, prostaglandins are widely used in clinic as first-line drugs.Pfizer IncThe original latan prostaglandin, which entered China in 1999, has maintained the dominant position in the market of intraocular pressure lowering drugs. The effect of prostaglandins on lowering intraocular pressure is achieved through pressure-independent aqueous humor outflow, that is, aqueous humor enters the space of the ciliary muscle from the ciliary body visible under the gonioscope, and then into the suprachoroidal space, which is latent and its pressure is zero. theoretically, as long as the anterior chamber pressure is greater than zero, aqueous humor can flow out through this way.

OT-301 of Okangwei is a nitric oxide donor bemeprost analogue, which activates primary and secondary aqueous humor outflow when decomposed into nitric oxide and bemeprostaglandin. Bemeprost stimulates aqueous humor outflow from uveosclera and nitric oxide stimulates aqueous humor outflow from trabecular meshwork. This dual mechanism stimulates aqueous humor outflow through the uveal sclera.

Data from the phase II clinical trial of the drug in the United States showed that in the head-to-head trial with latanoprost, all concentrations of OT-301 (0.021%, 0.042% and 0.065%) reached the predetermined primary efficacy endpoint relative to latanoprost (0.005%) according to the decrease in average daytime intraocular pressure relative to the baseline at week 4 follow-up. The intraocular pressure lowering effect of OT-301 (0.065%) was statistically superior to latanoprost. For 0.021%, 0.042% and 0.065% doses of OT-301, compared with latanoprost's 7.4mm Hg, the average intraocular pressure reduction from the average daytime intraocular pressure baseline on the 28th day was 7.8mm Hg, 8.2mm Hg and 8.7mm Hg, respectively. In the pre-designated secondary analysis for the reduction of mean daytime intraocular pressure from the baseline, OT-301 (0.065%) reached a statistically superior secondary end point over latanoprost on day 7 and day 14, in addition to day 28. In the pre-designated secondary efficacy analysis, compared with latanoprost, the 0.065% dose of OT-301 showed statistical superiority in the reduction of intraocular pressure from the baseline at all three time points on day 28, with a difference of up to 1.4mm Hg. On the 28th day, compared with an average of 7.4mm Hg in the latanoprost group, 44% of patients treated with OT-301 (0.065%) reduced their average intraocular pressure from the baseline to 1 mm Hg or more, 37% to 2 mm Hg or more, 27% to 3 mm Hg or more, 16% to 4 mm Hg or more, and 12% to 5 mm Hg or more. In terms of safety, only 16.8% of the subjects had adverse reactions of conjunctival congestion, while many adverse reactions occurred when other prostaglandins were used alone, OT-301 was well tolerated as a whole, and there were no serious adverse events or systemic side effects.

Source: Frost Sullivan Analysis, Ojai Vision prospectus

According to the Oukangwei prospectus, OT-301 will conduct two phase Ⅲ clinical trials in China, which will evaluate the safety and efficacy of OT-301 in patients with open-angle glaucoma or ocular hypertension. In particular, it has been proved that 0.065% or 0.1% concentration of OT-301 is not inferior to or better than 0.005% concentration of latanoprost eye drops and is well tolerated at 12 months during administration.