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HuidaGene Therapeutics Announces IND Active for the Multinational Trial of HG004 to Treat Inherited Blindness

2023.01.28 11:41
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  • HG004 is a one-time, direct-to-RPE treatment of inherited retinal disease caused by mutations in the RPE65 gene

  • ∼ 10-fold lower vector doses than other AAV2 gene therapy clinical trials to be tested in this planned trial

  • On track to initiate the multi-national trial by H1-2023

SHANGHAI and CLINTON, N.J., Jan. 27, 2023 /PRNewswire/ -- HuidaGene Therapeutics (HuidaGene), a clinical-stage
biotechnology company developing CRISPR-based programmable genomic medicine, announces that the US. Food
and Drug Administration (FDA) has cleared its investigational new drug (IND) application for the planned multi-national
clinical trial of HG004 for the treatment of patients suffering from RPE65 mutation-associated inherited retinal
dystrophies, a group of genetic diseases caused by the mutations in RPE65 gene affecting the retina and passed on to
the children.

"We are thrilled to have received the IND clearance of our HG004 program from US FDA, marking our first IND clearance
as a company and our first retinal disorder program to reach clinical development stage," said Xuan Yao, Ph.D., Cofounder and Chief Executive Officer of HuidaGene. "Clearance of this IND is a testament to the in-house pipeline
development capabilities and high-quality preclinical data supporting HG004, as well as the strong CMC and analytics
capabilities through our partnership with WuXi Advanced Therapies. The goal of the HG004 program is to develop a
one-time, non-AAV2 gene replacement therapy to restore, treat, and prevent blindness of children and adults
with severe visual impairment or blindness due to RPE65 mutation-associated retinopathies globally."
Investigational HG004 is a novel ophthalmic injection that is being developed to treat RPE65 retinopathies. Based on
the head-to-head preclinical comparison study of HG004 and adeno-associated virus serotype 2 (AAV2) at the same
dose, the recovery of the retinal functions was increased by 67.6% (HG004) and 35.8% (AAV2 products) when compared
to the wild-type mice in the Rpe65 knockout murine model at Week 17 after a single injection. Therefore, HG004
demonstrates better transduction efficiency of the retinal pigment epithelium (RPE) compared with AAV2 and has the
potential to lower the total vector doses, which may reduce the risk of AAV vector-associated immunogenicity or ocular
adverse events in humans.

"We are excited by the promise of HG004 to offer a potential transformative treatment better than AAV2-mediated gene
replacement therapy," said Hui Yang, Ph.D., Co-Founder and Chief Scientific Advisor of HuidaGene. "Our extensive
preclinical studies demonstrated superior transduction efficiency and substantial restoration of vision loss at the RPE
layer when HG004 compared to AAV2 through our independently-developed Rpe65 gene knockout murine disease
model, which is found to mimic the retinal phenotypes and functions of patients with RPE65 mutation-associated
inherited retinal dystrophies."

"Our preclinical data supported our planned multi-national clinical trial with a starting effective dose far lower than the
approved AAV2-hRPE65 gene therapy product and with less volume need to be injected into the retina," said Dr. Xuan
Yao. "We had already enrolled patients at the end of 2022 in our investigator-initiated trial (IIT) in China, and we saw a
substantial restoration of vision that were progressing toward complete blindness even with nearly 25-fold lower vector
doses of HG004 than the approved AAV2-hRPE65 gene therapy product within seven days after the single-injection of

About Multi-national Clinical Trial of HG004
HG004 will be evaluated in a multinational, multicenter, multiple-cohort, dose-finding study of adult and pediatric
subjects with RPE65 retinopathies under one master protocol in different countries. The purposes of the study are to
evaluate the safety, tolerability, efficacy, and long-term clinical durability of a single injection of HG004 for up to 52
weeks. Primary endpoints include adverse events, certain laboratory measures, and ophthalmic examinations. The study
will also assess visual function via a multiluminance mobility test (MLMT), where subjects will navigate a mobility course
under various light levels. After completing the primary study period, subjects will continue to be assessed in a longterm follow-up study of HG004.

About RPE65 Mutation-Associated Inherited Retinal Dystrophies

Inherited retinal dystrophies (IRDs) are a group of rare blinding conditions caused by mutations in any 1 of more than
250 genes. Leber's congenital amaurosis (LCA), severe early childhood-onset retinal dystrophy (SECORD), early-onset
severe retinal dystrophy (EOSRD), and retinitis pigmentosa (RP), which may all be grouped under the heading of RPE65
mutation-associated inherited retinal dystrophies, are considered to represent a phenotypic continuum of the same
disease. The RPE65 mutation-associated inherited retinal dystrophies with a typical onset between birth and five years
of age exhibit several common clinical findings, chiefly night blindness (light staring with profound nyctalopia and
nystagmus), progressive loss of visual fields, and loss of central vision. The percentage of patients (with biallelic RPE65
mutations) meeting the World Health Organization (WHO) criteria for blindness increased with age and reached 100%
after the age of 40 years. Given the often severe and early visual loss associated with RPE65 inherited retinal
dystrophies, other areas of development, including speech, social skills, and behavior, may also be delayed.

About HuidaGene
HuidaGene Therapeutics is a global clinical-stage biotechnology company focusing on discovering, engineering, and
developing CRISPR-based genetic medicine 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, otology, myology, and neurology. 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.

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