Company: MBIO
Filing Date: 2025-04-01
Form Type: 424B3
Source: 0001104659-25-030657
Chunk: 16

Company: MUSTANG BIO, INC.
Filing Date: 2025-04-01
Form: 424B3
Chunk 16
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 accounting for approximately 52% of malignant primary brain and CNS tumors and approximately 14% of
all primary brain and CNS tumors. On average during the years 2017 through 2021, more than 13,000 new cases of GBM were diagnosed per
year in the U.S. While GBM is a rare disease, with only 3.3 cases per 100,000 persons per year in the U.S., it is quite lethal, with a
median survival of only 9 months. Standard of care therapy for patients less than 70 years of age consists of maximal surgical resection,
radiation, chemotherapy with temozolomide, and alternating electric field therapy. This front-line regimen has remained relatively unchanged
for the last 20 years due to the failure of novel therapies to improve survival, and there is no standard of care whatsoever for recurrent
GBM.

Immunotherapy approaches targeting brain tumors
offer promise over conventional treatments. IL13Rα2 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 (TCM)
or enriched CD62L+ naïve and memory T cells (TN/MEM) are isolated and enriched. Our
manufacturing process limits ex vivo expansion, which is designed to reduce T