HuidaGene Therapeutics Announces First Patient Dosed Of The World's First Novel CRISPR/Cas13 RNA-Editing Therapy HG202 For Neovascular Age-related Macular Degeneration

·   HG202 is the first clinical program of high fidelity CRISPR/Cas13 RNA-editing therapy independently-developed by HuidaGene.

·   HG202 uses a single AAV vector delivering CRISPR/Cas13 RNA-editing tool to specifically knock-down VEGF-A mRNA levels.

·   HG202 efficiently inhibits choroidal neovascularization than existing therapies such as Aflibercept antibodies in head-to-head preclinical comparison studies.

SHANGHAI and CLINTON (NJ), Sept 6, 2023 – HuidaGene Therapeutics (辉大基因, "HuidaGene"), a global clinical-stage biotechnology company focused on developing CRISPR-based programmable genomic medicines, today announced that the first patient has been dosed in the SIGHT-I clinical trial of the world's first RNA-editing therapy HG202 by Prof. XiaoRong Li and his team in Tianjin Medical University Eye Hospital for the treatment of neovascular age-related macular degeneration (nAMD).

HG202 is a novel CRISPR/Cas13 RNA-targeting therapy packaging in one-single adeno-associated viral (AAV) vector independently-developed by HuidaGene's proprietary HG-PRECISE^® platform to target and knockdown the expression of VEGF-A mRNA within the local retina. This HG202 therapy is designed to treat nAMD patients who have developed resistance to anti-VEGF treatment as well as patients who are responsive to current standard anti-VEGF therapies.

"We are pleased to have successfully enrolled our first patient of HG202, which is an important milestone of HuidaGene evaluating the safety and efficacy of its world-leading, China-first CRISPR/Cas13-mediated RNA editing therapy in humans," said Xuan Yao, Ph.D., Co-Founder, President, and General Manager for Greater China of HuidaGene. "HG202 is HuidaGene's first fully independent innovative CRISPR gene-editing pipeline product using our novel high-fidelity CRISPR/Cas13Y (hfCas13Y) developed by HG-PRECISE^® platform with not only efficiently knocks down the mRNA expression level of the target gene but essentially no collateral cleavage activity with high level of safety. With its strong ability to develop and optimized gene-editing tools, the team of HuidaGene first discovered the Cas13X/Y system, the smallest RNA editing tool at present which was published in Nature Methods 2021 (http://www.nature.com/articles/s41592-021-01124-4), and on this basis, further developed a high-fidelity Cas13Y (hfCas13Y) with efficient editing and very low off target activities which was also published in Nature Biotechnology 2022 (http://www.nature.com/articles/s41587-022-01419-7), laying out the technical foundation of the CRISPR/Cas13 system for the future clinical applications." 

"Currently, there is no treatment for patients with nAMD who are non-responsive and have developed tachyphylaxis to existing anti-VEGF therapies, representing an important unmet clinical need," commented by Alvin Luk, Ph.D., M.B.A., C.C.R.A., Co-Founder and CEO of HuidaGene. "Even for those patients who are responsive to anti-VEGF therapies, it requires frequent intraocular injections to maintain their vision due to the short half-life of these drugs. A one-time 'once-and-done' treatment such as HG202 can transform the treatment paradigm for nAMD, particularly up to 30-40% of patients with nAMD do not respond at all or are resistant to any standard anti-VEGF therapies as published in New England Journal of Medicine.  Therefore, we're excited about the potential of HG202 to treat drug-resistant and non-resistant nAMD patients."

About Neovascular Age-Related Macular Degeneration (nAMD)

Age-related macular degeneration (AMD) is one of the leading causes of blindness globally in adults aged 50 and older if left untreated. Nearly 190 million people over the age of 60 worldwide are living with nAMD, and the condition will affect even more people around the world as the global population ages. Neovascular age-related macular degeneration (nAMD), recognized as the most common late stage of AMD, accounts for approximately 10% of all AMD cases, resulting in 80-90% of legal blindness caused by AMD. nAMD is characterized by abnormal growth of blood vessels in the choroid (a part of the eye containing blood vessels that nourish the retina) under the macular of the retina leading to loss of vision and can rapidly progress over weeks if untreated. Current anti-vascular endothelial growth factor (anti-VEGF) therapies that target extracellular VEGF have significantly changed the landscape for the treatment of nAMD, becoming the golden standard-of-care. These therapies, however, have short half-lives, which necessitates life-long monthly or bimonthly repeated intraocular injections to maintain efficacy. However, majority of nAMD patients have suboptimal responses with persistent fluid or recurrent exudation still occurs despite standardized anti-VEGF therapy.

About SIGHT-I Trial of HG202 in nAMD

This open-label, multi-center, dose-finding investigator-initiated trial (SIGHT-I) is designed to evaluate the safety, tolerability, and efficacy of high-fidelity CRISPR-Cas13 RNA-editing therapy targeting knock-down of VEGF-A (HG202) in patients with nAMD who are either non-responsive or responsive to previous anti-VEGF treatments. The primary endpoint of the trial is safety and tolerability of HG202 at different doses after a single administration. Secondary endpoints include changes in best-corrected visual acuity (BCVA), measurement of central retinal thickness (CRT), and the need for anti-VEGF rescue injections. Two leading retinal centers (Tianjin Medical University Eye Institute and Shanghai Eye and ENT Hospital of Fudan University) in China are participating in this SIGHT-I clinical trial for HG202. For more information, please contact: HG20201@huidagene.com

About HuidaGene - 辉大基因 

HuidaGene Therapeutics (辉大基因) is a global clinical-stage biotechnology company focusing on discovering, engineering, and developing novel gene-editing tools and gene therapies to rewrite the future of genomic medicine. Based in Shanghai and New Jersey, HuidaGene is committed to addressing patients' needs globally with various preclinical therapeutic programs covering ophthalmology and neurology. We are currently advancing clinical programs of HG004 in inherited retinal disease caused by RPE65 mutations (which has been granted both ODD and RPDD by US FDA), HG202 in neovascular age-related macular degeneration, and our preclinical pipeline, including programs in retinitis pigmentosa, neuro-developmental disease of MECP2 duplication syndrome, neuromuscular diseases of Duchenne muscular dystrophy, and neuro-otology of hereditary hearing loss. Company's CRISPR-based therapeutics offer the potential to cure patients with life-threatening conditions by repairing the cause of their disease. HuidaGene is committed to transforming the future of genome-editing medicine.

For more information, please visit http://www.huidagene.com 

or follow us on LinkedIn at http://www.linkedin.com/company/huidagene