Company: MBIO
Filing Date: 2025-01-15
Form Type: S-1
Source: 0001410578-25-000028
Chunk: 139

Company: MUSTANG BIO, INC.
Filing Date: 2025-01-15
Form: S-1
Chunk 139
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 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 generations of CAR-T cells. Our academic partners at COH have recently completed the treatment phase of their Phase 1 study, which was designed to assess the feasibility and safety of using T CMor T N/MEMenriched IL13Rα2-specific CAR-engineered T cells for clinical study participants with IL13Rα2 recurrent/refractory malignant glioma (ClinicalTrials.gov Identifier: NCT02208362). In this study, COH enrolled and treated 65 patients, with 58 patients receiving 3 cycles of CAR T cells per the study protocol. In March 2024, results from this study were published in Nature Medicine. Preliminary data indicated that the CAR-T cells were well tolerated, and no dose-limiting toxicities were observed in any of the study arms nor where there any occurrences of CRS or treatment-related deaths. Of the 58 patients evaluable for disease response, 50% achieved stable disease (SD) or better; 22%, including 8 patients with grade 4 gliomas, achieved SD or better for at least 90 days. Two patients achieved partial response, and one patient achieved complete response on the study. In 2016 COH reported that a patient had achieved a complete response to treatment based on the imaging and clinical features set forth by the Response Assessment in Neuro-Oncology Criteria (“RANO”). This result was published as a