Genespire’s “Immune-Shielded” Gene Therapy Receives Dual FDA and EC Orphan Designations for Rare Metabolic Disorder

MILAN —January 20, 2026— Italian biotech Genespire has reached a major regulatory milestone for its lead candidate, GENE202, receiving Orphan Drug Designation from both the U.S. Food and Drug Administration (FDA) and the European Commission (EC). The therapy is aimed at treating Methylmalonic Acidemia (MMA), a devastating pediatric metabolic disorder that currently lacks any approved disease-modifying treatments.

The ISLV Breakthrough: Lifelong Enzyme Production

Unlike many current gene therapies that utilize AAV vectors—which can be diluted as a child’s liver grows—GENE202 utilizes Genespire’s proprietary Immune Shielded Lentiviral Vector (ISLV) platform. Developed by gene therapy pioneers Prof. Luigi Naldini and Dr. Alessio Cantore, this “off-the-shelf” approach offers several distinct advantages:

• Immune Evasion: The “shielding” technology is designed to mask the vector from the immune system, allowing for safe intravenous administration without triggering the severe inflammatory responses often seen in systemic gene delivery.

• Genomic Integration: As a lentiviral vector, it integrates the functional MMUT gene directly into the DNA of the patient’s liver cells (hepatocytes).

• Pediatric Advantage: Because the gene is integrated, it is passed down to new cells as the liver grows, potentially enabling a true one-time, lifelong cure for infants and children.

Addressing a Fatal Metabolic Gap

Methylmalonic Acidemia (MMA) is caused by a deficiency in the methylmalonyl-CoA mutase (MMUT) enzyme, which is essential for breaking down certain proteins and fats. Without it, toxic metabolites like methylmalonic acid accumulate, leading to:

• Organ Damage: Progressive failure of the kidneys, liver, and heart.

• Neurological Impact: Severe developmental delays, seizures, and strokes.

• High Mortality: Frequent metabolic crises that can be fatal even with strict dietary management.

A Growing Sector: Funding and Partnerships

The dual orphan designations—which provide market exclusivity and fee waivers—arrive as Genespire prepares for clinical entry in late 2026. The company is well-capitalized following a €46.6 million ($52M) Series B in late 2024. This momentum reflects a broader industry resurgence in metabolic gene therapies, highlighted by recent high-value deals like the Regeneron-Tessera collaboration ($275M) and AAVantgarde Bio’s $141M Series B.