AAVantgarde begins dosing in Phase 1/2 LUCE-1 study for Usher Syndrome type 1B retinitis pigmentosa

AAVantgarde Bio, an Italian global biotechnology firm, revealed that it has initiated its LUCE-1 trial, a Phase 1/2 clinical study designed to evaluate the safety and tolerability of AAVB-081. This trial uses the company's proprietary dual hybrid gene therapy platform to deliver the MYO7A protein to patients with retinitis pigmentosa linked to Usher Syndrome Type 1B (USH1B). The technology behind this dual-AAV system for large gene delivery was developed by Prof. Alberto Auricchio at the Telethon Institute of Genetics and Medicine (TIGEM) in Naples, which is managed by the Telethon Foundation. AAVantgarde is a spin-off from TIGEM and holds the exclusive license for this technology for inherited retinal diseases.

The first subretinal gene therapy procedure in the LUCE-1 study took place under the guidance of Prof. Francesca Simonelli, the Head of Ophthalmology at the University Hospital of Campania “Luigi Vanvitelli” in Naples, one of three clinical sites participating in this trial. Prof. Simonelli serves as the global Chief Investigator for the study, which is the primary dosing site.

Prof. Simonelli expressed her enthusiasm about being the Principal Investigator in this pioneering Phase 1/2 clinical trial of AAV-081 for patients with USH1B-related retinitis pigmentosa. She emphasized that this innovative program aims to transform understanding and treatment for these underserved patients, with the potential to produce robust evidence that will advance scientific knowledge and directly impact patient care.

Dr. Jayashree Sahni, Chief Medical Officer of AAVantgarde, highlighted the honor of collaborating closely with Prof. Simonelli in this first-in-human clinical trial. She acknowledged Prof. Simonelli's significant expertise in developing gene therapies for ophthalmology and stressed the goal of swiftly bringing this novel therapy to the USH1B patient community.

Prof. Alberto Auricchio, the Founder and Chief Scientific Officer of AAVantgarde, shared his excitement about their dual hybrid technology being clinically tested for an ophthalmology indication. He expressed hope that the extensive research efforts would prove beneficial for patients with significant unmet needs.

Dr. Natalia Misciattelli, CEO of AAVantgarde, also conveyed her honor in having Prof. Simonelli as the Principal Investigator for this clinical study. She noted that the trial aims to provide hope for USH1B patients who currently have no therapeutic options to prevent vision loss. Dr. Misciattelli highlighted Prof. Simonelli's pioneering role in gene therapy for ophthalmology and her invaluable experience in the successful development of this innovative therapy.

AAVB-081 is an intra-retinal gene therapy product based on AAV8 vectors, designed to target MYO7A-associated Usher Syndrome (USH1B). The dual hybrid platform uses two AAV8 vectors, each carrying one half of the MYO7A gene expression cassette. These halves recombine within the cell nucleus to form a single gene, resulting in the production of therapeutic protein levels in animal models.

The LUCE-1 trial is a Phase 1/2 multicenter, open-label, dose-escalation study. It aims to investigate the safety, tolerability, and preliminary efficacy of three dose levels of dual AAV8.MYO7A (AAVB-081) administered subretinally to subjects with retinitis pigmentosa associated with Usher Syndrome Type 1B.

Usher Syndrome Type 1B (Usher1B) is an inherited disorder affecting the retina and inner ear, caused by mutations in the MYO7A gene. This gene is too large to fit inside a standard AAV vector, which presents a challenge for gene therapy. Approximately 20,000 individuals in the U.S. and E.U. suffer from Usher1B. These patients are born deaf, experience vestibular dysfunction, and begin to progressively lose vision during their first decade of life. While surgical treatments exist for deafness, there are currently no treatments available for the progressive vision loss and blindness associated with this condition.

AAVantgarde Bio is a clinical-stage international biotechnology company based in Italy. It has developed two proprietary Adeno-Associated Viral (AAV) vector platforms to overcome the gene therapy cargo capacity limitations of standard AAV vectors. These platforms are designed to deliver large genes to both ocular and non-ocular tissues. Co-founded by Prof. Alberto Auricchio at TIGEM and the Telethon Foundation, AAVantgarde aims to validate its platform in clinical settings for two inherited retinal diseases with significant unmet need.