HG004 / HuidaGene Therap - LARVOL DELTA

Results from LIGHT, a first-in-human AAV9-gene replacement therapy trial of HG004, in children and adults with RPE65-associated Leber’s congenital amaurosis (ESGCT 2024) - P1, P1/2 | "Although an adeno-associated virus serotype 2 (AAV2) gene therapy (voretigene neparvovec-rzyl; Luxturna) has been approved by the FDA and EMA in 2017 and 2018, respectively, AAV2 may not be an ideal vector to transduce the retinal pigment epithelial (RPE) cells than other serotypes such as AAV9. These three doses (25-, 15-, and 7.5-fold lower than the approved AAV2-hRPE65 gene therapy in the Phase 3 trial) in this LIGHT trial showed comparable results, suggesting that HG004 may potentially be a safer and more efficacious alternative treatment option for LCA2. HG004 is also being evaluated in a multi-regional clinical trial (NCT05906953) and granted both Orphan Drug Designation and Rare Pediatric Disease Designation by the U.S. FDA."

Clinical • First-in-human • P1 data • Gene Therapies • Inflammation • Inherited Retinal Dystrophy • Ocular Inflammation • Pediatrics • Retinal Disorders

HG004 Gene Therapy Reduces Chorioretinal Atrophy and Demonstrates Superior Retinal Safety Over Luxturna Clinical Settings (ASGCT 2025) - P1, P1/2 | "The LIGHT trial demonstrates that HG004 significantly mitigates the risk of progressive chorioretinal atrophy commonly observed with Luxturna. Retinal atrophy with HG004 is confined to retinotomy sites and remains non-progressive, emphasizing the benefits of enhanced RPE tropism, lower dosing, and optimized surgical techniques to provide a safer alternative for LCA2 patients. These findings underscore the critical role of vector design and delivery optimization in improving gene therapy safety profiles for IRDs."

Clinical • Gene therapy • Gene Therapies • Inflammation • Inherited Retinal Dystrophy • Ophthalmology • Pediatrics • Retinal Disorders

Comparative Analysis of Chorioretinal Atrophy in the LIGHT Study Versus Real-World Luxturna Studies (ARVO 2025) - P1, P1/2 | "Purpose Chorioretinal atrophy, a progressive side effect following subretinal Luxturna administration, affects a subset of patients and may impact therapeutic efficacy. This work highlights how advances in gene therapy can improve safety and effectiveness for people with rare genetic conditions. By addressing key challenges in current treatments, HG004 could set a new standard for safe and effective gene therapies, offering hope to those at risk of losing sight."

Clinical • Real-world • Real-world evidence • Inherited Retinal Dystrophy • Ophthalmology • Retinal Disorders

Leber Congenital Amaurosis Inherited Blindness of Gene Therapy Trial(LIGHT) (clinicaltrials.gov) - P1 | N=9 | Active, not recruiting | Sponsor: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2024 ➔ Oct 2028 | Trial primary completion date: Jan 2024 ➔ Oct 2024

Enrollment closed • Gene therapy • Trial completion date • Trial primary completion date • Gene Therapies • Inherited Retinal Dystrophy • Ophthalmology

AAV gene replacement therapy for RPE65‐mediated inherited retinal dystrophies (ESGCT 2023) - "Currently, our preliminary clinical data demonstrates a substantial restoration of vision that was progressing toward complete blindness even the starting dose level of HG004 is only 1/25 of Luxturna in Phase 3 clinical trial. Notably, neither adult nor pediatric patients receiving HG004 experienced serious adverse events or retinal detachments."

Gene Therapies • Inherited Retinal Dystrophy • Pediatrics

Preliminary Safety and Efficacy of HG004 Gene Therapy Trial for Leber's Congenital Amaurosis Associated with Mutations in RPE65 Gene (ASGCT 2024) - P1, P1/2 | "Most of the treated subjects had at least a 2-log unit increase in pupillary light responses with durable effects during follow-up. There is no retinal detachment or drug-related serious adverse events, suggesting subretinal gene therapy at lower total volume (200 µL) is safe. These three doses (25-,15-, and 7.5-fold lower than the approved AAV2-hRPE65 gene therapy in the Phase 3 trial) in this LIGHT trial showed comparable results, suggesting that HG004 may be a safer and more efficacious alternative treatment option for LCA2."

Clinical • Gene therapy • Gene Therapies • Inflammation • Inherited Retinal Dystrophy • Ophthalmology • Pediatrics • Retinal Disorders

Preclinical Studies of HG004 Gene Replacement Therapy in Support of Clinical Trial for RPE65-Associated Inherited Retinal Dystrophy (ASGCT 2024) - P1/2 | "Our results across all mouse studies demonstrated dose-responsive restoration of retinal function after the treatment of HG004 with a durable effect in mice for at least 34 weeks after the treatment of HG004. Furthermore, HG004 is safe for use in NHPs. The nonclinical studies supported the evaluation of HG004 in patients with RPE65-IRD."

Preclinical • Gene Therapies • Inherited Retinal Dystrophy • Pediatrics

HG004 Gene Therapy for Patients with Leber Congenital Amaurosis (ARVO 2024) - P1, P1/2 | "The preliminary data on 6 months at the low dose and 3 months at the middle dose of HG004 in a total of 6 LCA2 patients showed significant improvement in visual and retinal functions. These two doses (25- to 15-fold lower than the approved AAV2-hRPE65 gene therapy in the Phase 3 trial) in this LIGHT trial showed comparable results, suggesting HG004 may potentially be the best-in-class AAV gene therapy for LCA2. Currently, HG004 is being evaluated in a multi-regional clinical trial (NCT05906953) and has been granted both Orphan Drug Designation and Rare Pediatric Disease Designation by the U.S. FDA."

Clinical • Gene therapy • Inherited Retinal Dystrophy • Ophthalmology • Retinal Disorders

In-vivo Validation of HG004 Gene Replacement Therapy for Inherited Blindness (ARVO 2024) - "Our findings highlight the significant therapeutic potential of HG004 in restoring the function of RPE and photoreceptor cells with durability for at least 34 weeks in Rpe65-/- mice. Furthermore, our toxicology results in NHPs indicate that HG004 is well-tolerated with a good safety profile. These results strongly support the potential benefit of HG004 in treating RPE65-IRD."

Preclinical • Inherited Retinal Dystrophy • Ophthalmology

Safety and Efficacy Trial of HG004 for Leber Congenital Amaurosis Related to Rpe65 Gene Mutations (STAR) (clinicaltrials.gov) - P1/2 | N=20 | Recruiting | Sponsor: HuidaGene Therapeutics Co., Ltd.

Gene therapy • Trial completion date • Trial primary completion date • Gene Therapies • Inherited Retinal Dystrophy • Ophthalmology • Retinal Disorders

Safety and Efficacy Trial of HG004 for Leber Congenital Amaurosis Related to Rpe65 Gene Mutations (clinicaltrials.gov) - P1/2 | N=20 | Recruiting | Sponsor: HuidaGene Therapeutics Co., Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Gene therapy • Gene Therapies • Inherited Retinal Dystrophy • Ophthalmology • Retinal Disorders

Leber Congenital Amaurosis Inherited Blindness of Gene Therapy Trial(LIGHT) (clinicaltrials.gov) - P1 | N=9 | Recruiting | Sponsor: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Gene therapy • New P1 trial • Gene Therapies • Inherited Retinal Dystrophy • Ophthalmology • Retinal Disorders

Leber Congenital Amaurosis Inherited Blindness of Gene Therapy Trial (LIGHT) (clinicaltrials.gov) - P1 | N=9 | Recruiting | Sponsor: HuidaGene Therapeutics Co., Ltd.

Gene therapy • New P1 trial • Gene Therapies • Inherited Retinal Dystrophy • Ophthalmology • Retinal Disorders