Mustang Bio, Inc. has received a significant boost in its fight against aggressive brain cancers, with the U.S. Food and Drug Administration (FDA) granting Orphan Drug Designation to its investigational therapy, MB-101. This designation applies to MB-101, an IL13Ra2-targeted CAR T-cell therapy, specifically for the treatment of recurrent diffuse and anaplastic astrocytomas and glioblastoma (GBM). This is a crucial step forward for patients facing these rare and devastating diseases, as Orphan Drug status is reserved for therapies targeting conditions affecting fewer than 200,000 people in the U.S., offering incentives like tax credits and seven years of market exclusivity upon approval.

What makes Mustang Bio's approach particularly innovative is its strategy to combine MB-101 with MB-108, an HSV-1 oncolytic virus that had previously received its own Orphan Drug Designation for malignant glioma. This combined regimen, dubbed MB-109, aims to overcome a major challenge in cancer immunotherapy: "cold" tumors, which lack sufficient immune cell infiltration and are typically resistant to CAR T-cell therapies. The MB-108 oncolytic virus is designed to be injected first into the tumor, where it infects and lyses cancer cells, effectively "heating up" the tumor microenvironment (TME) by recruiting endogenous immune cells like CD8+ and CD3+ T-cells. This inflamed TME then ideally allows the subsequent administration of MB-101 CAR T-cells to better infiltrate the tumor mass, become activated, and more effectively eliminate cancer cells.

Early data from an ongoing Phase 1 trial of MB-101, published in Nature Medicine, supports this promising approach. The therapy was well-tolerated, and notably, 50% of patients achieved stable disease or better, with two patients experiencing remarkable complete responses lasting 7.5 and over 66 months, respectively. These impressive results were observed particularly in patients whose tumors already showed higher levels of immune cell infiltration (were "hot") prior to MB-101 treatment. This strong preclinical and early clinical evidence validates Mustang Bio's novel combination strategy, reflecting their deep commitment to finding effective solutions for these challenging-to-treat cancers and potentially offering new hope to patients with limited treatment options.