Neurophth Therapeutics Receives IND Clearance to Initiate Clinical Trial for China AAV-ND4 Gene Therapy NR082 in Leber Hereditary Optic Neuropathy

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WUHAN, China and SAN DIEGO, Jan. 19, 2022 /PRNewswire/ -- Neurophth Therapeutics, Inc., (hereinafter referred to as "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 NR082 (rAAV2-ND4), the first of its kind in China, for the treatment of Leber hereditary optic neuropathy (LHON) associated with ND4 mutation.

(PRNewsfoto/Neurophth Therapeutics, Inc.)
(PRNewsfoto/Neurophth Therapeutics, Inc.)

"LHON is a rare and maternally inherited mitochondrial genetic disease of blindness for which there are no effective treatments," said Bin Li, M.D., Ph.D., Founder and Chairman of Neurophth. "Researchers and clinicians have been 'sharpening a sword for ten years' with the persistence of finding a cure for these patients globally- a dream that is dearest to my heart. NR082 may provide hope to blind patients and families with LHON where currently none exists. I believe this makes NR082 the first China AAV gene therapy for LHON to enter clinical trials in the U.S."

"My colleagues and I have worked on multiple INDs initiated from the U.S. or Europe, but this is the first in-vivo AAV gene replacement therapy originated from China," said Alvin Luk, Ph.D., M.B.A., C.C.R.A., Chief Executive Officer at Neurophth. "The FDA clearance to advance our first investigational gene therapy, NR082, into clinical development is a significant milestone for the community of gene therapy, and also moving Neurophth one step closer to delivering our mission of in China for global to bring transformative treatments to patients living with rare ocular diseases."

Investigational NR082, a novel recombinant adeno-associated viral serotype 2 vector (rAAV2) containing a codon-optimized of NADH-dehydrogenase subunit 4 (ND4) gene, is a novel ophthalmic injection that is being developed for the treatment of Leber hereditary optic neuropathy (LHON) associated with ND4 mutations. Safety and efficacy of ND4 gene therapy have been demonstrated in three investigator-initiated trials (IITs) as well as clinical durability up to 90 months at 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 in improving visual acuity[1],[2],[3]. The Food and Drug Administration (FDA) granted orphan-disease designation in the US to NR082 in September 2020[4].

"Now that the NR082 IND is active, we look forward to advancing clinical development of NR082 in the US, which has the potential to positively impact the lives of patients by restoring their visions," said Xin Zhang, M.D., M.Sc., Chief Medical Officer and Chief Operations Officer at Neurophth. "We are eager to initiate the enrollment of our US clinical trial this year, which will be a historic milestone as the first ever China originated AAV gene therapy clinical trial in the US. With this IND clearance by the FDA, we are embarking on a new pathway of care through this innovative gene therapy."

"NR082 represents numerous firsts in the AAV gene therapy space and underscores Neurophth's commitment to patient-first and operational excellence," said Yiyuan Chen, M.Sc., Head of Global Regulatory Affairs of Neurophth. "NR082 is the first China AAV gene therapy for the LHON to receive ODD from the U.S. FDA. In addition, this is the first of all China AAV gene therapy products to get an IND approval from the U.S. FDA."

About Leber's Hereditary Optic Neuropathy (LHON)

Leber hereditary optic neuropathy (LHON) is a maternally inherited blinding bilateral optic atrophy[5] with a prevalence of around 1 in 31,000 to 1 in 54,000 particularly in young adult males[6]. 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[5],[7],[8]. 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[8]. Thus, the pathophysiology of LHON is characterized by selective loss of RGCs and their axons, which leads to rapidly progressive bilateral vision loss. The visual prognosis is poor, and most patients progress to vision worse than 20/200 within the first year after disease onset[7]. There is currently no approved effective treatment for LHON and the current treatment remains limited[9].

About Neurophth

Neurophth is China's first 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 198 subjects with investigational gene therapies in the retina. Our most advanced investigational candidate, NR082, in development for the treatment of ND4-mediated LHON, has been granted orphan drug designation (ODD) by the U.S. FDA and its IND has also been approved by the China NMPA in March 2021 and by the U.S. FDA in January 2022. The clinical trial has been in progress since June 2021. The pipeline also includes ND1-mediated LHON, autosomal dominant optic atrophy, optic neuroprotection (e.g., glaucoma), vascular retinopathy (e.g., diabetic retinopathy), and five other preclinical candidates. Neurophth has initiated the scaling up in-house manufacturing process in single-use technologies to support future commercial demand at the Suzhou facilities. To learn more about us and our growing pipeline, visit


1. Wan X, Pei H, Zhao MJ, et al. Efficacy and safety of rAAV2-ND4 treatment for Leber's hereditary optic neuropathy. Scientific Report, 2016; 6:21587.

2. Yang S, Ma SQ, Wan X, et al. Long-term outcomes of gene therapy for the treatment of Leber's hereditary optic neuropathy. EBioMedicine, 2016; 10:258-268.

3. Yuan JJ, Zhang Y, Liu H, et al. Seven-year follow-up of gene therapy for Leber's hereditary optic neuropathy. Ophthalmology, 2020; 127(8): 1125-1127.

4. Press release from Neurophth.

5. Carelli V, Carbonell M, deCoo IF, et al. International consensus statement on the clinical and therapeutic management of Leber hereditary optic neuropathy. Journal of Neuroophthalmology, 2017; 37: 371-381.

6. Meyerson C, Van Stavern G, Mcclelland C. Leber hereditary optic neuropathy: current perspectives. Clinical Ophthalmology, 2015; 9:1165-1176.

7. Yu-Wai-Man P, Votruba M, Burte F, et al. A neurodegenerative perspective on mitochondrial optic neuropathies. Acta Neuropathology, 2016; 132: 789-806.

8. Newman NJ, Lott MT, Wallace DC. The clinical characteristics of pedigrees of Leber's hereditary optic neuropathy with the 11778 mutation. American Journal of Ophthalmology, 1991; 111: 750-762.

9. Jurkute N, Harvey J, Yu-Wai-Man P. Treatment strategies for Leber hereditary optic neuropathy. Current Opinion of Neurology, 2019; 32: 99-104.


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