X-linked severe combined immunodeficiency (XSCID) is a rare genetic disorder that occurs in 1-2 per 100,000 births. For almost 20 years, investigators have been conducting clinical trials with ex vivo gene therapy for XSCID either as an alternative to HSCT or following a poor outcome post-HSCT. St. Jude Children’s Research Hospital has developed a safety modified lentiviral (LV) vector which is currently being investigated in a multicenter clinical trial in conjunction with reduced-exposure busulfan conditioning for newly diagnosed infants with XSCID. A similar trial is being conducted with this vector at the National Institutes of Health (NIH) in patients over the age of two with persistent disease after one or more haploidentical HSCTs. Both trials continue to accrue patients, with patients under the age of two being treated at St. Jude, UCSF Benioff Children’s Hospital San Francisco and Seattle Children’s Hospital, and older patients being treated at the NIH.
CD123 is over expressed in 75-89% of AML pateints and over 90% in Blastic plasmacytoid dendritic cell neoplasm (BPDCN) patients. There were an estimated 19,520 new U.S. cases of AML in 2018 with an estimated 25% 5-year survival rate. BPDCN is an ultra rare disease and aggressive blood cancer with 500-1,000 patients per year in the U.S. and a median overall survival of 9-12 months. MB-102 has shown promising response rates in early small populations of these patients in a physician IND study out of City of Hope.
CD20 is a membrane-embedded surface molecule which plays a role in the differentiation of B-cells into plasma cells. There were an estimated 74,680 new U.S. cases B-cell Non-Hodgkin Lymphoma in 2018 with an estimated 70% 5-year survival rate. MB-106 has been optimized as a 3rd generation fully human antibody and is currently in a physician IND Study trial in B-cell non-Hodgkin lymphoma (NHL) patients.
CS1 cell receptors regulate immune functions and are overexpressed in Multiple Myeloma (MM). There were an estimated 30,770 new U.S. cases in 2018 with an estimated 50% 5 year survival rate. A lead optimized candidate has been selected and is undergoing GMP lentiviral production for clinical trials.
IL-13Rα2 is a GBM restricted receptor expressed abundantly on over 75% of GBM patients. There are approximately 30,000 newly diagnosed GBMs annually worldwide with only a 5% 5-year survival rate. MB-101 has shown a promising early response rate in a first patient in a physician IND study out of City of Hope.
MB-103 are autologous HER2-specific CAR-modified virus-specific T cells (VSTs). There were an estimated 12,760 new cases worldwide in 2018 with an estimated 30% 2-year survival rate. MB-103 has been fully optimized as a fully human HER2 CAR T and is currently in clinical studies at City of Hope.
MB-105 is a prostate stem cell antigen that has the potential to address a broad range of solid tumors including: Prostate Cancer with an annual incidence of 164,000; Pancreatic Cancer with an annual incidence of 55,000; Gastric cancer with an annual incidence of 26,000; and Bladder Cancer with an annual incidence of 81,000. MB-105 is in pre-clinical optimization and is expected to be ready for clinical studies in mid-2019.
C134 is a next-generation oncolytic herpes simplex virus (“oHSV”) that can replicate in tumor cells, but not in normal cells. Replication of C134 in the tumor itself not only kills the infected tumor cells but causes the tumor cell to act as a factory to produce new virus. In February 2019, Mustang Bio entered into a licensing agreement with nationwide children’s hospital for the treatment of glioblastoma multiforme, an aggressive form of brain cancer that has an incidence of two to three per 100,000 adults per year, and accounts for 52 percent of all primary brain tumors. A Phase 1 clinical trial for MB-108 is scheduled to commence in the first half of 2019.