Genespire Shares Positive Preclinical Data at ASGCT Meeting

Genespire, a biotechnology firm specializing in off-the-shelf gene therapies for pediatric genetic diseases, has announced promising preclinical data at the 27th Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT) in Baltimore, MD, USA. The data presented validates the efficacy of Genespire’s liver-directed lentiviral gene therapy in a mouse model of methylmalonic acidemia (MMA). This abstract has garnered the ASGCT Excellence In Research Award.

MMA is a rare genetic metabolic disorder caused by defects in the gene encoding the mitochondrial enzyme methylmalonyl-coA mutase (MUT). This defect hampers the breakdown and utilization of proteins and fats, leading to the accumulation of methylmalonic acid in the body. High levels of this acid can damage vital organs such as the brain, liver, and kidneys. Currently, no targeted drugs are approved for MMA, leaving patients with significant morbidity and a drastically reduced life expectancy.

In the study presented at ASGCT, researchers administered an integrative immune shielded lentiviral vector (ISLV) encoding a human MUT transgene intravenously in a mouse model of MMA. The results were highly encouraging: the treated mice showed a rapid, substantial, and long-lasting reduction in circulating methylmalonic acid levels. This effect lasted for over a year, accompanied by normalization of weight and complete survival of the mice. Additionally, ISLV administration led to a systemic reduction of methylmalonic acid not only in the liver but also in the brain and kidney, indicating an extrahepatic benefit through liver-mediated detoxification.

This groundbreaking work was carried out by Dr. Elena Barbon and Dr. Alessio Cantore at the San Raffaele Telethon Institute for Gene Therapy (SR-Tiget) in collaboration with Genespire. Dr. Barbon received the ASGCT Excellence In Research Award for this abstract, which is awarded to the top 15 abstracts from ASGCT members or associate members.

Alessio Cantore, Group Leader at SR-Tiget and co-founder of Genespire, emphasized the significance of these findings, stating, "These compelling data provide evidence for the efficacy, safety, and extrahepatic benefit of our integrative immune shielded lentiviral vector (LV)-based gene therapy and important preclinical validation."

Julia Berretta, CEO at Genespire, also commented on the achievement, stating, "Receiving the ASGCT Excellence In Research Award provides further external validation on the quality of our research and promise of our technology.” She added, “We believe that our unique ISLV gene therapy approach, allowing for stable gene transfer and long-lasting expression of the therapeutic gene, may be optimally positioned to treat MMA patients."

Genespire is dedicated to developing gene therapies based on immune shielded lentiviral vectors for pediatric patients with genetic diseases. These therapies are designed for intravenous use, enabling life-long production of the therapeutic gene directly from the patient's liver. Initially, the company is advancing treatments for inherited metabolic diseases with high unmet medical needs.

Based in Milan, Italy, Genespire was founded in March 2020 by gene therapy pioneers Prof. Luigi Naldini and Dr. Alessio Cantore, in collaboration with Fondazione Telethon and Ospedale San Raffaele. Genespire is a spin-out of SR-Tiget, a leading cell and gene therapy research institute.