HuidaGene Therapeutics Receives the First-Ever FDA Clearance of CRISPR/Cas13 RNA-Editing HG202 for Macular Degeneration

• HG202 is the first CRISPR/Cas13Y RNA-targeting therapy to enter clinical development and the only clinical-stage CRISPR RNA-editing therapy for age-related macular degeneration

• Preclinical studies in laser-induced CNV mice showed HG202 reduced CNV area by 87%, outperforming both anti-VEGF antibodies and AAV-anti-VEGF gene therapy

SHANGHAI and CLINTON (NJ), November 4, 2024—HuidaGene Therapeutics (“HuidaGene”), a global clinical-stage biotechnology company developing genome medicines, today announced that the US FDA has cleared its HG202 investigational new drug (IND) application for neovascular age-related macular degeneration (nAMD). HG202 is the first-ever clinical-stage CRISPR/Cas13 RNA-editing and the only clinical-stage RNA-targeting therapy for nAMD.

“This open IND for HG202 by the US FDA – the first regulator to have cleared CRISPR/Cas13 for clinical development – represents an important milestone for HuidaGene and the entire CRISPR gene-editing field of RNA editing,” said Alvin Luk, Ph.D., M.B.A., C.C.R.A., Co-founder and Chief Executive Officer of HuidaGene.  “We chose to go to the FDA because HG202 demonstrated good results in the in-vitro, in-vivo preclinical studies and first-in-human ‘SIGHT-I’ trial. In September 2023, we dosed the world’s first novel CRISPR/Cas13 RNA-editing therapy in humans, and we recently presented preliminary data at the ARVO, ASGCT, EURETINA, and ESGCT this year. The rigor of our clinical data in China using a non-receptor binding pathway approach through Cas13 RNA editor to partially knock down the mRNA expression of VEGFA brings the potential to AMD patients.”

Xin Zhang, M.D., MSc., Chief Operations Officer and Chief Medical Officer of HuidaGene, added, “Up to 46% of AMD patients using anti-VEGF reagents have shown poor response or have developed tachyphylaxis with anti-VEGF therapies, resulting in irreversible vision loss. AMD patients deserve safe and effective treatment options. This is a critical step toward overcoming the challenges of AMD patients who have failed anti-VEGF therapies. In the proposed BRIGHT clinical trial, we aim to explore safety and efficacy trends at different doses of HG202. We look forward to beginning enrollment soon.”

“My team and I first discovered the Cas13X/Y system through our AI/ML-driven HG-PRECISE^®  platform, which is less than 800aa, suitable for single AAV delivery(published in Nature Methods 2021),” said Hui Yang, Ph.D., Co-Founder and Chief Scientific Advisor of HuidaGene. “Based on this basis, my team and I further developed a high-fidelity Cas13Y (hfCas13Y) with efficient editing and very low off-target activities, which was also published in Nature Biotechnology 2022, laying out the technical foundation of the CRISPR/Cas13 system for future clinical applications.”

About ‘BRIGHT’ Trial (NCT06623279)

This open-label, multicenter, Phase 1, dosing finding trial (an open-laBel, dose-escalation study for CRISPR/Cas13-RNA targetInG tHerapy for the Treatment of neovascular age-related macular degeneration, BRIGHT) is designed to evaluate the safety and tolerability of high-fidelity CRISPR-Cas13 RNA-editing therapy targeting knock-down of VEGF-A mRNA (HG202) in patients with nAMD, affecting nearly 190 million people over the age of 60 worldwide. The primary endpoint of the trial is the safety and tolerability of HG202 at different doses after a single administration. Secondary endpoints include changes in best-corrected visual acuity (BCVA), central retinal thickness (CRT) measurement, and the need for anti-VEGF rescue injections. For more information, please contact: HG20202@huidagene.com.

About HuidaGene

HuidaGene utilizes its proprietary CRISPR-based HG-PRECISE^® platform to develop potentially curative genome medicines. 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) for 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. 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.