Our candidate product targets X-linked Hyper IgM Syndrome (X-HIGM or CD40 Ligand Deficiency), the most common form of Hyper IgM Syndrome. X-HIGM is a rare and potentially life-threatening immune deficiency disorder. Patients with Hyper IgM are at significant risk for opportunistic infections, recurrent bacterial and viral infections, and cancer, with a median life expectancy of less than 30 years. Generally, patients incur recurrent infections, and often exhibit normal or elevated levels of IgM antibodies, and low or absent IgG, IgE and IgA antibodies, due to a failure of the mutated CD40L to bind CD40 on B-cells. The current standard of care consists in life-long immunoglobulin replacement therapy and antibiotics to prevent deadly lung infections. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only known cure. However, donors are only available for about 1/3 of the patients, and HSCT is associated with severe side effects, and potential complications. The CD40 Ligand gene needs to be tightly regulated. If not, abnormal and unwanted lymphoproliferation is likely to occur and therefore untargeted gene replacement therapies are not adapted for this disease.

Genespire’s Advanced Gene Editing approach consists of rescuing functional expression of the endogenous defective CD40L gene in the T-cells of the patients thus maintaining its physiological expression control, with the aim of substantially improving the immune response of patients, and their quality of life.