Neurophth’s Ophthalmic Gene Therapy NR082 Receives FDA Orphan Drug Designation for LHON

On September 24, Neurophth Therapeutics, a wholly-owned subsidiary of Neurophth Biotechnology, announced that its ophthalmic gene therapy NR082 (NFS-01 program) has been granted Orphan Drug Designation by the U.S. FDA for the treatment of Leber’s Hereditary Optic Neuropathy (LHON) caused by ND4 mutations. According to publicly available information from Neurophth Biotechnology, this is the company’s first candidate drug developed, having previously completed a global, large-sample clinical trial of gene therapy for LHON.

Dr. Lu Yingming, CEO of Neurophth, stated, “The significance of orphan drug designation lies in the regulatory recognition of unmet clinical needs for rare diseases such as Leber Hereditary Optic Neuropathy (LHON). This designation for NR082 will, to some extent, reduce R&D investment costs and accelerate the progress of clinical trials and market approval registration. Neurophth is committed to fundamentally addressing the underlying cause and improving patients’ quality of life through one-time gene therapy treatments.”

Leber’s Hereditary Optic Neuropathy (LHON) is a rare maternally inherited mitochondrial disorder characterized by degeneration of retinal ganglion cells, leading to irreversible vision loss and even blindness. The disease primarily affects adolescents and young adults. Patients with LHON typically experience sudden loss of central vision in one eye, followed by involvement of the other eye. It is a symmetric condition with poor functional visual recovery. Within less than one year, 97% of patients lose vision in both eyes, and 25% of patients experience simultaneous bilateral vision loss.

Genetic sequencing has revealed that Leber’s hereditary optic neuropathy (LHON) is typically caused by the m.11778G>A mutation in mitochondrial DNA, which affects the NADH dehydrogenase subunit 4 (ND4) gene. This mutation impairs the mitochondrial respiratory chain, leading to ATP deficiency, oxidative stress in retinal ganglion cells, and subsequent apoptosis. Currently, there are no effective treatments or cures for LHON available in clinical practice, indicating a significant unmet medical need.

According to publicly available information, in the NFS-01 project, scientists used recombinant adeno-associated virus as a vector to deliver the correct human ND4 gene via intravitreal injection to damaged retinal ganglion cells in patients, thereby repairing the mitochondrial respiratory chain and restoring the vitality and visual function of retinal ganglion cells.

Neurophth initiated an exploratory clinical trial of NR082 gene therapy in China in 2011. The results showed that among the nine patients with LHON caused by ND4 mutations who participated in the trial, seven experienced significant improvement in vision, with best-corrected visual acuity recovering to 0.8. The mean best-corrected visual acuity improved by 0.39 logMAR (equivalent to nearly four lines on the Snellen chart) across all nine patients. Eight patients completed long-term follow-up for nearly eight years, with no serious adverse events reported. These clinical findings were published in the journal *Ophthalmology* in 2020.

Based on the positive results from preclinical studies, Professor Li Bin’s team completed an international gene therapy clinical trial involving 159 patients with Leber hereditary optic neuropathy (LHON) in China and Argentina between 2017 and 2018. The latest progress of this trial was also presented at the American Society of Gene & Cell Therapy (ASGCT) 2020 Annual Meeting, held online.

In a previously released press release, Professor Li Bin stated that the reason gene therapy has “made significant strides” in the treatment of ocular diseases lies in the unique characteristics of the eye: as a closed spherical structure, it allows for localized intraocular injection of drugs with minimal systemic impact, making it well-suited for gene therapy. Furthermore, more than 220 genes are associated with ophthalmic conditions, and mutations in any of these genes can lead to vision loss and blindness. Practice has demonstrated that gene therapy, which utilizes safe viral vectors to deliver nucleic acid therapeutics for correcting genetic abnormalities or expressing normal gene products, represents one of the promising strategies for treating blinding eye diseases.

Neurophth, founded in 2016, is a Chinese ophthalmic gene therapy R&D company. Its co-founders are Professor Li Bin, Dr. Xiao Su, and Mr. Cai Dabo. In 2018, Neurophth secured angel-round financing, led by Miracle Light (a subsidiary of BGI), with participation from Mint Angel Fund and Northern Light Venture Capital. This April, the company completed an RMB 130 million Series A financing round, led by Sequoia Capital China and Fosun Star Future Capital, with follow-on investment from Northern Light Venture Capital.

A press release previously issued by Neurophth stated that the company, leveraging Leber’s Hereditary Optic Neuropathy (LHON) as its entry point, has completed a global large-sample clinical trial of gene therapy for LHON and is expanding into the field of gene therapy for other genetic diseases. Currently, the company is advancing several product candidates in both clinical and preclinical stages.

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