The lentiviral gene-therapy method employed in MB-207 was co-developed by scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and St. Jude Children’s Research Hospital (St. Jude). MB-207 has been studied at NIAID since 2012 and continues to be assessed in a NIAID-supported Phase 1/2 clinical trial for XSCID in patients over the age of two who have received prior HSCT. Mustang expects to file an investigational new drug application (IND) with the FDA to initiate a multi-center pivotal Phase 2 clinical trial of MB-207 in this patient population in the fourth quarter of 2020.
X-linked severe combined immunodeficiency (XSCID) is a rare genetic disorder that occurs in approximately 1 per 225,000 births. It is characterized by the absence or lack of function of key immune cells, resulting in a severely compromised immune system and death by 1 year of age if untreated. Patients with XSCID have no T-cells or natural killer cells. Although their B-cells are normal in number, they are not functional. As a result, XSCID patients are usually affected by severe bacterial, viral or fungal infections early in life and often present with interstitial lung disease, chronic diarrhea and failure to thrive. Among patients who receive HSCT, many are unable to establish adequate T-cell immunity or lose T-cell immunity over time. Further, approximately two-thirds of patients who receive HSCT lack sufficient B-cell immunity and need lifelong immunoglobulin replacement therapy.
The specific genetic disorder that causes XSCID is a mutation in the gene coding for the common gamma chain (γc), a protein that is shared by the receptors for at least six interleukins. These interleukins and their receptors are critical for the development and differentiation of immune cells. The gene coding for γc is known as IL-2 receptor gamma, or IL2RG. Because IL2RG is located on the X-chromosome, XSCID is inherited in an X-linked recessive pattern, resulting in almost all patients being male.