Genespire Presents Positive Preclinical Dosing Data for In Vivo Gene Therapy for Methylmalonic Acidemia

MILAN, ITALY – May 14, 2025 – Genespire, a biotechnology company focused on off-the-shelf gene therapies for pediatric genetic diseases, presented promising preclinical data on dosing for its first-in-human in vivo liver-directed gene therapy for methylmalonic acidemia (MMA). The oral presentation took place late yesterday at the 28th Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT) in New Orleans, USA.

The study evaluated the intravenous administration of an immune-shielded lentiviral vector (ISLV) encoding a human MUT transgene in a mouse model of MMA. Researchers demonstrated that the ISLV gene therapy effectively treated MMA in these models by delivering a functional MMUT gene to liver cells. A codon-optimized version (ISLV.MMUTco) showed greater efficacy at lower doses compared to the wild-type vector. Testing three different doses revealed dose-dependent improvements, with even the lowest dose showing benefits due to the selective advantage of treated cells. Studies in humanized mouse models indicated that CD47-enriched vectors achieved comparable efficacy at substantially lower doses, informing potential human-compatible dosing. These findings support the progression of this ISLV-based gene therapy towards clinical trials for MMA patients.

The research was conducted by Dr. Elena Barbon and Professor Alessio Cantore at the San Raffaele Telethon Institute for Gene Therapy (SR-Tiget) in collaboration with Genespire.

Professor Alessio Cantore commented on the significance of the data presented at ASGCT, highlighting its further preclinical validation for their immune-shielded lentiviral vector (LV)-based gene therapy as they advance towards the clinic.

Genespire’s CEO, Karen Aiach-Pignet, noted that these data will be instrumental in determining the dosing level for their anticipated Phase I clinical trial of GENE202 next year. She also expressed excitement about the momentum in the in vivo gene therapy field, particularly following the recent acquisition of EsoBiotec by AstraZeneca.

Genespire is developing a novel proprietary class of lentiviral vectors, ISLVs, with its lead candidate GENE202 nearing clinical development for the treatment of methylmalonic acidemia (MMA), a severe genetic disorder affecting the metabolism of specific amino acids and fats.