Company: MBIO
Filing Date: 2025-02-05
Form Type: S-1/A
Source: 0001104659-25-009408
Chunk: 137

Company: MUSTANG BIO, INC.
Filing Date: 2025-02-05
Form: S-1/A
Chunk 137
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-19-year-olds in the U.S. While GBM is a rare disease 2-3 cases per 100,000 persons per year in the U.S. and European Union (“EU”), it is quite lethal, with five-year survival rate historically under 10%, which has been virtually unchanged for decades. Standard of care therapy consists of maximal surgical resection, radiation, and chemotherapy with temozolomide, which, while rarely curative, is shown to extend median overall survival from 4.5 to 15 months. GBM remains difficult to treat due to the inherent resistance of the tumor to conventional therapies.

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Immunotherapy approaches targeting brain tumors offer promise over conventional treatments. IL13R α2 is an attractive target for CAR T therapy, as it has limited expression in normal tissue but is overexpressed on the surface of greater than 50% of GBM tumors. CAR-T cells are designed to express membrane-tethered IL-13 receptor ligand (“IL-13”) mutated at a single site (glutamic acid at position 13 to a tyrosine; E13Y) with high affinity for IL13Rα2 and reduced binding to IL13Rα1 in order to reduce healthy tissue targeting (Kahlon KS et al. Cancer Research.2004;64:9160-9166). We are developing an optimized CAR-T product incorporating enhancements in CAR-T design and T cell engineering to improve antitumor potency and T cell persistence. These include a second-generation hinge-optimized CAR containing mutations in the IgG4 linker to reduce off-target Fc interactions (Jonnalagadda M et al. Molecular Therapy.2015;23(4):757-768.), a 4-1BB (CD137) co-stimulatory signaling domain for improved survival and maintenance of CAR T cells, and the extracellular domain of CD19 as a selection/tracking marker. In order to further improve persistence, either central memory T-cells (T CM) or enriched CD62L+ naïve and memory T cells (T N/MEM) are isolated and enriched. Our manufacturing process limits ex vivoexpansion, which is designed to reduce T cell exhaustion and maintain a T CMor T N/MEMphenotype. Based on experiments with CAR-Ts in mouse xenograft models of GBM, these CAR-modified T CMand T N/MEMcells have been shown to be more potent and persistent than earlier