HuidaGene Presents Late-Breaking Data at World Muscle Society 2024 Demonstrating HG302 CRISPR/hfCas12Max DNA-Editing Therapy for Duchenne Muscular Dystrophy to Support M.U.S.C.L.E. Clinical Trial

HG302, a single AAV system packaging the compact, high-fidelity Cas12Max, meditates a single-cut in-vitro genome editing efficiency of over 60% in the human DMD exon 51 splice-donor.Systemic delivery of HG302 in humanized DMD mice efficiently restored dystrophin expression and rescued motor function, including rotarod and grip strength tests, to wild-type levels.HG302 induced therapeutically acceptable editing efficiency at the exon 51 splice-donor site in non-human primates with no observed drug-related toxicity.M.U.S.C.L.E.（an open-label, Multidose dose-escalation study to Understand the Safety of Crispr gene-editing therapy and its long-Lasting Effects in DMD） is the world’s first-in-human CRISPR/DNA genome-editing trial beyond Cas9 for DMD. SHANGHAI and CLINTON (NJ), September 24, 2024 - HuidaGene Therapeutics (“HuidaGene”), a global clinical-stage biotechnology company developing potentially curative genome medicines, today announced the presentation of the CRISPR/hfCas12Max® supporting the clinical development of HG302 to treat Duchenne muscular dystrophy (DMD) as a late-breaking abstract at the 29th Annual Congress of the World Muscle Society, taking place in Prague, Czechia, from October 8 to 12, 2024. The novel high-fidelity Cas12i variant (hfCas12Max) discovered through HuidaGene’s proprietary AI-guided HG-PRECISE® platform exhibits the highest on-target editing efficiency and lowest off-targeting activity in mammalian cells compared to widely used SpCas9 or other Cas12a/b/e systems while packaging into a single viral vector. The USPTO granted Cas12i a patent with strong intellectual property protection. Systemically delivered by a single ‘all-in-one’ AAV system, HG302 induced the hfCas12Max-mediated single-cut genome editing in human DMD exon 51 splice-donor sites with a one-time intravenous injection to treat DMD patients. HG302 CRISPR-based DNA-editing therapy has been granted both orphan drug and rare pediatric disease designations for treating DMD patients amenable to exon 51 skipping by the U.S. FDA. Details on late-breaking abstract:Title: 719LP - Duchenne Muscular Dystrophy Gene Editing Therapy with CRISPR/high-fidelity Cas12MaxLocation/Date: The Prague Congress Centre, Forum Hall - 11th October 2024 “Several industry-sponsored AAV-mediated micro-dystrophin gene replacement therapy trials observed serious adverse events, including liver toxicity, myocarditis, thrombocytopenia, and death at high doses ranging from 1.3E14 to 3E14 vg/kg,” said Alvin Luk, Ph.D., MBA, CCRA, Co-Founder and Chief Executive Officer of HuidaGene. "Our high editing efficiency and minimal off-target activity of hfCas12Max allow us to dose HG302 at the E13 vg/kg range, a 10-fold lower than current ongoing DMD clinical trials. The M.U.S.C.L.E. clinical study (NCT06594094) currently recruits ambulant DMD boys with measurably impaired muscle function.” About HuidaGene HuidaGene utilizes its proprietary CRISPR-based HG-PRECISE® platform to discover, engineer, and develop genome medicine. The Company is advancing clinical programs of HG004 (granted ODD & RPDD by FDA) ‘LIGHT’ trial (NCT06088992) and Phase 1/2 international, master-protocol ‘STAR’ clinical trial (NCT05906953) in RPE65-associated inherited retinal disease, HG202 RNA-editing therapy ‘SIGHT-I’ trial (NCT06031727) for neovascular age-related macular degeneration, HG204 RNA-editing therapy (granted ODD & RPDD by FDA and ODD by EMA) ‘HERO’ trial for MECP2 duplication syndrome, as well as HG302 DNA-editing therapy (granted ODD & RPDD by FDA) first-in-human ‘MUSCLE’ trial (NCT06594094) for Duchenne muscular dystrophy, and the preclinical pipeline, including HG303 DNA-editing for Amyotrophic Lateral Sclerosis, and CRISPR RNA-editing therapy for Alzheimer’s disease. HuidaGene’s extensive intellectual property portfolio positions it as a leader in unleashing the full potential of genome medicines for neurology and ophthalmology. Learn more at huidagene.com or on LinkedIn.

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