MT-ND1

WUHAN, China and SAN DIEGO, March 7, 2023 /PRNewswire/ -- Matthias Szabo Zarb, a Maltese college student, was diagnosed with Leber hereditary optic neuropathy caused by ND1 mutation (ND1-LHON) two years ago, which led to a rapid deterioration in his visual acuity and inability to engage in normal activities. Through the National Alliance for Rare Diseases Support, he learned about NFS-02, a gene therapy drug targeting ND1-LHON which is developed by the Chinese ophthalmic gene therapy company, Neurophth. Following a recommendation from the Embassy of China in Malta, Ms. Michelle Muscat, the chairman of the Malta National Alliance for Rare Diseases Support, contacted Neurophth. Neurophth decided to donate NFS-02 and recommended Dr. Yong Zhang, director of ophthalmology center at Taihe Hospital, as the treating physician. Upon arrival, the patient received free expedited genetic tests supported by Neurophth. On March 4th, representatives of Neurophth donated NFS-02 to the Maltese patient at Taihe Hospital. Notably, Professor Zhang Yong performed the surgery for the patient on the same day. The Embassy of China in Malta expressed their gratitude to Neurophth for their support in treating international patients. They praised the company for donating drug to Mr. Matthias Szabo Zarb and his family, as well as fostering closer ties between China and Malta. The collaboration has received high attention from the Maltese government. The National Alliance for Rare Diseases Support organized a press conference where the Speaker of the Maltese Parliament delivered a speech. Former Maltese Prime Minister Muscat and his wife also conveyed their appreciation to the embassy. In 2017, Professor Li Bin, the former director of the Ophthalmology Department of Tongji Hospital of Huazhong University of Science and Technology, launched the world's largest sample size clinical trial for gene therapy for ND4-LHON. The study included 149 patients from China and 10 patients from Argentina. The 12-month follow-up results showed that NFS-01 has remarkable curative effect and no obvious serious adverse events have been found. NFS-02 is Neurophth's second gene therapy, in development for the treatment of mtND1-mediated LHON. After six years of development, the company's technology platform has become more advanced. NFS-02 has been used to treat multiple patients in the investigator-initiated clinical trial (IIT) in China and received orphan drug designation and IND approval from the U.S. FDA. Logo - SOURCE Neurophth Therapeutics, Inc.

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 . SOURCE Neurophth Therapeutics, Inc.

WUHAN, China and SAN DIEGO, Sept. 27, 2022 /PRNewswire/ -- Neurophth Therapeutics, Inc. ("Neurophth") announced today that the first patient has been dosed in Phase III clinical trial for the treatment of Leber hereditary optic neuropathy (LHON). Neurophth is conducting a Phase I/II/III, multi-center, two-parts study aimed at evaluating the safety, tolerability, and efficacy of NR082 in LHON patients with ND4 mutations. The Investigational New Drug (IND) application of NR082 has been approved by CDE on March 29, 2021. Wenbin Wei, vice president of Beijing Tongren hospital affiliated to Capital Medical University, completed the first dose in the Phase III clinical trial. Prof. Wenbin Wei, vice president of Beijing Tongren hospital, CMU, commented, "As a clinician, I share the same expectation of LHON patients for effective and affordable treatments. NR082 has shown promising safety and efficacy data in all clinical work to date and is officially advanced into a Phase III trial. Ophthalmic gene therapy is coming of age. We hope that NR082 will be available soon, making a life-changing difference to patients by technological innovation." Professor Bin Li, Founder, Chairman and CEO of Neurophth, said, " Dosing the first participants in Phase III trial is a significant milestone of Neurophth and a positive sign of the booming of ophthalmic gene therapy industry. Our team will continue to make every effort to accelerate the clinical trials and commercialization process of China's first ophthalmic gene therapy. We believe that NR082 will have positive results of Phase III clinical trial, delivering a solution that can transform the lives of LHON patients in return for their years of waiting." "There is currently no approved effective treatment for LHON. NR082 leverage gene therapy strategy and use recombinant adeno-associated virus as the vector to deliver the correct genes to the patients' damaged optic ganglion cells, thus restore the vitality and visual function of optic ganglion cells." Dr. Xiaoning Guo, Chief Medical Officer of Neurophth, said, "The Phase III clinical trial is a breakthrough in the ophthalmic gene therapy industry. Neurophth will advance the Phase III clinical trial in hope that safe and effective therapy can soon liberate patients from the darkness." 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 NR082 Investigational NR082 (rAAV2-ND4), a novel recombinant adeno-associated viral vector, serotype 2, containing a mitochondria codon-optimized NADH-dehydrogenase subunit 4 (ND4) 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-disease designation to NR082 in September 2020. Safety and efficacy of mtND4 gene therapy have been evaluated in three investigator-initiated trials (IITs) with clinical durability up to 90 months in the first IIT. The results of these three IITs of 186 LHON patients demonstrated that an intravitreal injection of rAAV2-ND4 in subjects with LHON is well tolerated and can be effective at improving visual acuity. 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. The pipeline also includes mtND1-mediated LHON (the Company's 2nd US ODD), 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 .