Mustang Bio, Inc. (Nasdaq: MBIO) has been granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA) for MB-108, a herpes simplex virus type 1 (HSV-1) oncolytic virus, for the treatment of malignant glioma. This designation provides Mustang Bio with significant benefits, including tax credits, prescription drug user fee waivers, and seven years of market exclusivity upon approval. The company plans to advance MB-108 in combination with MB-101, an IL13Rα2-targeted CAR-T cell therapy, as a potential treatment option for patients with malignant glioma, including recurrent glioblastoma (GBM) and high-grade astrocytomas.
Novel Therapeutic Strategy
Mustang Bio's therapeutic strategy involves combining MB-108 with MB-101 to address the challenges of treating malignant glioma. Preclinical data suggests that MB-108 can reshape the tumor microenvironment (TME), transforming 'cold' tumors into 'hot' tumors, which may enhance the efficacy of MB-101 CAR-T cell therapy. This approach aims to improve the infiltration and activation of CAR-T cells within the tumor mass, ultimately leading to more effective tumor cell killing.
Manuel Litchman, M.D., President and Chief Executive Officer of Mustang, stated, "The Orphan Drug Designation for MB-108 is significant for Mustang, as it could provide additional market exclusivity and we hope to advance MB-108, in combination with MB-101, as a potential treatment option for patients living with malignant glioma, including patients with recurrent glioblastoma (GBM) and high-grade astrocytomas, where there is historically a median overall survival of six months."
Clinical Trial Data and Outcomes
Previous clinical trials of MB-101 have shown promising results. Two patients treated solely with MB-101 who had high levels of intratumoral CD3+ T cells pre-therapy achieved complete responses lasting 7.5 and 31+ months, respectively. These complete responses were observed in the two patients with the 'hottest' tumors prior to treatment with MB-101 out of 53 patients in Phase 1 clinical trials. Phase 1 clinical trials of MB-101 at City of Hope and of MB-108 at The University of Alabama at Birmingham are ongoing.
Development Contingencies
Further development of the MB-109 program, which combines MB-101 and MB-108, is contingent upon securing additional funding and/or establishing a strategic partnership. The company's ability to advance this program depends on its financial resources and collaborative efforts.
About MB-109
MB-109 is Mustang’s designation for the treatment regimen combining MB-101 (IL13Rα2-targeted CAR-T cell therapy licensed from City of Hope) with MB-108 (HSV-1 oncolytic virus licensed from Nationwide Children’s Hospital). The combination is designed to leverage MB-108 to make cold tumors “hot” and potentially improve the efficacy of MB-101 CAR-T cell therapy. MB-108 oncolytic virus is first injected to infect tumor cells which, in turn, leads to reshaping of the TME through recruitment of endogenous CD8- and CD3-positive effector T-cells. This inflamed TME potentially permits MB-101 CAR-T cells injected into and around the tumor to better infiltrate into and throughout the tumor mass, undergo activation and, ideally, effect tumor cell killing.
