HuidaGene Therapeutics Announced First Patient Dosed in the HERO Clinical Trial of HG204 for MECP2 Duplication Syndrome

SHANGHAI and MIDDLETOWN (DE), December 6, 2024 –HuidaGene Therapeutics (“HuidaGene”), a global clinical-stage biotechnology company developing programmable genome medicines, today announced that the first patient had been dosed in the HERO clinical trial evaluating HG204, marking the initiation of the world’s first clinical evaluation of an RNA-editing therapy for the treatment of MECP2 duplication syndrome (MDS). This milestone signifies a major advancement in the development of therapies for this rare and debilitating neurodevelopmental disorder.

“We are thrilled to announce the dosing of the first patient in the HERO clinical trial, a key milestone in advancing innovative CRISPR/Cas13 RNA-editing therapies,” said Alvin Luk, Ph.D., M.B.A., C.C.R.A., CEO and co-founder of HuidaGene. “HG204 has the potential to provide a much-needed solution for MECP2 duplication syndrome, a condition with no approved disease-modifying therapies. This achievement reflects our commitment to addressing significant unmet medical needs in rare and fatal genetic disorders.”

HG204 is a groundbreaking CRISPR RNA-editing therapy utilizing a single adeno-associated virus vector to deliver HuidaGene’s proprietary high-fidelity RNA editor, hfCas13Y, and a guide RNA targeting the MECP2 gene. This innovative approach is designed to reduce MECP2 mRNA and protein levels, which are overexpressed due to genomic duplication of the Xq28 region. Preclinical studies demonstrated that HG204 achieves stable and durable expression in the brain tissue of mice and monkeys. In humanized mouse models of MDS, a single intracerebroventricular injection of HG204 led to significant improvements in motor skills, social behavior, and survival time.

“This first patient dosing represents years of dedication from our scientists and clinical teams, and we are committed to conducting the HERO trial with the highest scientific rigor,” added Xin Zhang, MD, Chief Operations Officer and Chief Medical Officer of HuidaGene. “HG204 represents an innovative approach to address the overexpression of MECP2, aiming to improve the quality of life for patients and their families.”

About HERO Trial of HG204 (NCT06615206)

The HERO (a first-in-Human trial to Evaluate a novel CRSPIR Rna-editing therapy, HG204, in patients with MDS, a rare Orphan disease) study conducted at Peking University First Hospital, is an open-label, multi-dose, first-in-human study designed to evaluate the safety, tolerability, and preliminary efficacy of HG204 in male patients aged 2 to 18 with genetically confirmed MDS. The study aims to optimize the balance between safety and efficacy by assessing initial and adjusted dosing cohorts. Key outcomes include improved motor, cognitive, and adaptive behavior and MECP2 mRNA and protein level reductions. The U.S. Food and Drug Administration (FDA) has granted HG204 Orphan Drug Designation and Rare Pediatric Disease Designation, and the European Medicines Agency (EMA) has also recognized it with ODD. These Designations highlight the urgent unmet medical need for therapies targeting MDS.

About MECP2 Duplication Syndrome

Methyl-CpG binding protein 2 (MeCP2) duplication syndrome (MDS) is a rare, fatal neurodevelopmental disorder caused by the duplication of the MECP2 gene, resulting in overexpression of the MeCP2 protein, which is an epigenetic regulator critical for normal brain development and maintenance of function. Symptoms include infantile hypotonia, severe intellectual disability, developmental delays, epilepsy, recurrent respiratory infections, loss of motor and speech skills, anxiety, and a shortened lifespan. MDS primarily affects males, with an estimated 50,000 to 100,000 cases worldwide. Approximately half of the patients succumb to complications before age 25. Currently, there are no approved disease-modifying therapies for MDS, and treatment options are limited to supportive care.

About HuidaGene 

HuidaGene utilizes its proprietary CRISPR-based HG-PRECISE^® platform to develop potentially curative genome medicine. The Company is advancing clinical programs, including trials of HG004 (granted ODD & RPDD by FDA) ‘LIGHT’ trial (NCT06088992) and Phase 1/2 international, master-protocol ‘STAR’ clinical trial (NCT05906953) in RPE65-associated retinal disease, HG202 RNA-editing therapy ‘SIGHT-I’ first-in-human trial (NCT06031727) and ‘BRIGHT’ Phase 1 clinical trial (NCT06623279) for nAMD, HG204 RNA-editing therapy (granted ODD & RPDD by FDA and ODD by EMA) ‘HERO’ trial (NCT06615206) for MECP2 duplication syndrome, and HG302 DNA-editing therapy (granted ODD & RPDD by FDA) first-in-human ‘MUSCLE’ trial (NCT06594094) for DMD. The preclinical programs include HG303 DNA-editing for ALS and CRISPR RNA-editing therapy for Alzheimer’s and Huntington’s Disease. With an extensive intellectual property portfolio, HuidaGene is a leader in genome medicines for neurology and ophthalmology. Learn more at huidagene.com or on LinkedIn.