HuidaGene Therapeutics Initiates M.U.S.C.L.E. Clinical Trial of HG302 for Duchenne Muscular Dystrophy and Completes First Patient Dosed

SHANGHAI and MIDDLETOWN (DE), December 12, 2024 –HuidaGene Therapeutics (“HuidaGene”), a global clinical-stage biotechnology company pioneering next-generation genome medicines, today announced the dosing of the first patient in its MUSCLE clinical trial evaluating HG302, a CRISPR-based DNA-editing therapy for Duchenne muscular dystrophy. The promising data from the preclinical studies in mice and monkeys were shared during the presentation of a late-breaking abstract at the 29th Annual Congress of the World Muscle Society in October in Prague, Czechia.

“This is a pivotal moment for HuidaGene and the field of gene editing,” said Alvin Luk, Ph.D., M.B.A., C.C.R.A., CEO and co-founder of HuidaGene. “While micro-dystrophin gene replacement therapies have raised concerns about its long-term clinical benefits, high-dose AAV-associated safety, and micro-dystrophin use, HG302 represents a fundamentally different approach. Powered by hfCas12Max, our CRISPR-based therapy achieves precise exon skipping with minimal off-target effects at significantly lower doses than current AAV-mediated micro-dystrophin therapies or dual-AAVs CRISPR-Cas9 DNA-editing and DNA base-editing therapies. Dosing the first patient in the MUSCLE trial underscores HG302’s potential to offer safer, more effective options for DMD patients and their families.”

HG302 utilizes HuidaGene’s proprietary hfCas12Max, a high-fidelity CRISPR nuclease developed through the AI-guided HG-PRECISE^Ò platform, offering superior on-target efficiency and minimal off-target activity (Yang H. et al., 2023, Protein & Cell). Packaged in a single “all-in-one” adeno-associated viral vector, HG302 precisely edits the DMD exon51 splice-donor site, enabling exon skipping to restore dystrophin production, which is designed as a one-time treatment option for DMD patients amenable to exon51 skipping or reframing. Unlike current high-dose AAV-mediated micro-dystrophin gene replacement therapies, which have been associated with severe adverse events such as liver toxicity, myocarditis, and thrombocytopenia, HG302 aims to be administered at a much lower dose, enabled by hfCas12Max’s superior editing efficiency and reduced off-target activity, minimizing the risk of immune-related adverse effects.

“Our approach with HG302 combines the precision of CRISPR DNA editing with a lower, safer dose profile, offering hope for a transformative treatment for DMD,” stated Xin Zhang, MD, Chief Operations Officer and Chief Medical Officer of HuidaGene. “The initiation of the MUSCLE trial is a critical milestone in our commitment to bringing this life-saving therapy to patients and their families, addressing the urgent need for safer and effective options in managing DMD.”

About MUSCLE Trial of HG204 (NCT06594094)

The MUSCLE (Multidose study to Understand the Safety of Crispr editing therapy and its long-Lasting Effects in DMD) trial conducted at Shanghai Children’s Medical Center affiliated with Shanghai Jiao Tong University School of Medicine, is an open-label, multidose dose-escalation, first-in-human study enrolling ambulatory boys between 4 and 8 years old with DMD who exhibit impaired muscle function. The study aims to evaluate the safety, tolerability, and preliminary efficacy of HG302. Key outcomes include dystrophin restoration, function muscle improvements, and quality of life metrics. The U.S. Food and Drug Administration (FDA) has granted HG302 Orphan Drug Designation and Rare Pediatric Disease Designation, emphasizing its potential to address significant unmet needs for DMD patients.

About Duchenne Muscular Dystrophy

Duchenne muscular dystrophy is a severe X-linked recessive disorder and a common type of progressive muscular dystrophy caused by mutations in the DMD gene, leading to the absence of functional dystrophin protein. Most children with DMD develop the disease between the ages of 3 and 5 and are usually asymptomatic during infancy. It affects approximately 1 in 3,500 boys worldwide, and early-stage patients may show signs of motor development, lagging behind children of the same age and unsteady walking, which are often mistaken for calcium deficiency or weak constitution and ignored. As the disease progresses, symptoms of muscle weakness become more and more severe, resulting in progressive muscle degeneration, loss of ambulation by adolescence, life-threatening complications in early adulthood, and shortened lifespan.

Current treatment options are limited to symptom management, and the clinical benefits of AAV micro-dystrophin gene replacement therapies are questionable.

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.