OTL-104

OTL-104 is an investigational autologous ex vivo hematopoietic stem cell (HSC) gene therapy being developed for the treatment of Crohn's disease in patients with biallelic mutations in the NOD2 gene, a subset known as NOD2 Crohn’s disease. The therapy uses a lentiviral vector to introduce a functional copy of the NOD2 gene into a patient’s own HSCs under control of a myeloid-directed chimeric promoter. These modified cells are then infused back into the patient, where they engraft and differentiate, restoring NOD2-dependent immune responses in tissue-resident macrophages and other cells of the hematopoietic system. Preclinical studies have shown that OTL-104 can fully restore NOD2 function in both human and mouse models deficient for this protein, supporting its potential as a one-time curative approach for this severe form of Crohn’s disease[1][2][3][5][6].