Neurophth Receives IND Clearance from FDA for AAV-ND1 Gene Therapy of LHON

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Dec 19, 2022, 08:00 ET

WUHAN, China and SAN DIEGO, Dec. 19, 2022 /PRNewswire/ -- Neurophth Therapeutics, Inc. ("Neurophth") today announced receiving the U.S. Food and Drug Administration (FDA) clearance of its investigational new drug (IND) application on the in-vivo gene replacement therapy NFS-02 (rAAV2-ND1), for the treatment of Leber hereditary optic neuropathy (LHON) associated with ND1 mutation.

Investigational NFS-02, a novel recombinant adeno-associated viral serotype 2 vector (rAAV2) containing a codon-optimized of NADH-dehydrogenase subunit 1 (ND1) gene, is a novel ophthalmic injection that is being developed for the treatment of Leber hereditary optic neuropathy (LHON) associated with ND1 mutations. The FDA granted orphan drug designation in the U.S. to NFS-02 in January 2022. The approved clinical trial is a multicenter, single-arm, open-labeled, dose-finding Phase I/II clinical study investigating the safety, tolerability, and efficacy of NFS-02 in LHON patients with ND1 mutations.

Professor Bin Li, Founder, Chairman and CEO of Neurophth, said, "We are thrilled to have received IND clearance for NFS-02, marking our second program to reach clinical development. Our first drug targets ND4-LHON, and this time we continue to advance our pipeline of ophthalmic gene therapy and develop drugs for patients with ND1-LHON, hoping that every patient can embrace a bright future."

"The approval of this IND marks a significant milestone for the Company. Based on encouraging preclinical data, we believe that this gene therapy drug candidate holds promise to become a safe and effective treatment for patients." said Xiaoning Guo, Ph.D., Chief Medical Officer of Neurophth, "We are excited to proceed with our NFS-02 clinical trial plans for treating ND1-LHON patients, and we look forward to initiate the enrollment of our US clinical trial early next year."

"The IND clearance from FDA marks a great recognition to our R&D capabilities." said Yiyuan Chen, Senior Vice President of Regulatory Affairs of Neurophth, "We are excited by the opportunity to bring gene therapy originated from China to patients and physicians in the U.S., highlighting our strategy of 'In China, for global'."

About Leber's Hereditary Optic Neuropathy (LHON)

Leber hereditary optic neuropathy (LHON) is a maternally inherited blinding bilateral optic atrophy with a prevalence of around 1 in 31,000 to 1 in 54,000 particularly in young adult males. There are three mitochondrial DNA point mutations account for about over 90% of all LHON cases, namely, G3460A in ND1, G11778A in ND4 and T14484C in ND6, with G11778A mutation in NADH-dehydrogenase subunit 4 (ND4) gene causing a ND4 subunit arginine to be incorrectly replaced by a histidine and reducing the activity of NADH dehydrogenase by 50-80% as being the most common mutation worldwide. These mutations affect complex I subunits of the mitochondrial respiratory chain, impairing mitochondrial function and increasing the production of reactive oxygen species. The retinal ganglion cells (RGCs) appear to be selectively vulnerable to mitochondrial dysfunction resulting in apoptotic cell death, optic nerve degeneration, and the development of optic atrophy. Thus, the pathophysiology of LHON is characterized by selective loss of RGCs and their axons, which leads to rapidly progressive bilateral vision loss. There is currently no approved effective treatment for LHON and the current treatment remains limited.

About NFS-02

Investigational NFS-02 (rAAV2-ND1), a novel recombinant adeno-associated viral vector, serotype 2, containing a mitochondria codon-optimized NADH-dehydrogenase subunit 1 (ND1) gene under the control of the cytomegalovirus promoter and enhancer, is a novel gene therapy product that is being developed for the treatment of Leber hereditary optic neuropathy (LHON) associated with mtND4 mutations. The U.S. Food and Drug Administration (FDA) granted orphan drug designation to NFS-02 in January 2021.

About Neurophth

Neurophth is China's leading in-vivo gene therapy company for ophthalmic diseases. With subsidiaries in China (Wuhan, Shanghai, and Suzhou) and US (San Diego, California), Neurophth, a fully integrated company, is striving to discover and develop genomic medicines for patients suffering from genetic diseases globally. Our validated AAV platform, which has been published in Nature - Scientific Reports, Ophthalmology, and EBioMedicine, has successfully delivered proof-of-concept investigator-initiated trials data of 186 subjects with investigational gene therapies in the retina. Our most advanced investigational gene therapy drug candidate, NR082 (rAAV2-ND4), in development for the treatment of mtND4-mediated LHON, has been granted orphan drug designation (ODD) by the U.S. FDA and EMA. After the IND clearance by the China NMPA in March 2021 and the U.S. IND by FDA in January 2022, the first patient has been dosed in the Phase III clinical trial in September 2022. Recently, our second gene therapy drug candidate NFS-02, has been granted IND clearance from U.S. FDA. The pipeline also includes autosomal dominant optic atrophy, optic neuroprotection, vascular retinopathy, and five other preclinical candidates. Neurophth has scaled up in-house manufacturing capability in Suzhou facility utilizing single-use technologies to support future commercial demand. To learn more about us and our growing pipeline, visit www.neurophth.com.