Mustang Bio, Inc. (Mustang or the Company) announced the first data from the indolent lymphoma cohort of the Company?s ongoing multicenter Phase 1/2 clinical trial evaluating MB-106, a first-in-class CD20-targeted, autologous CAR-T cell therapy for the treatment of relapsed or refractory B-cell non-Hodgkin lymphomas (B-NHL) and chronic lymphocytic leukemia (CLL), demonstrating clinical responses as well as safety and efficacy consistent with the ongoing Phase 1/2 clinical trial taking place at Fred Hutchinson Cancer Center (Fred Hutch). Initial data were presented by Mazyar Shadman, M.D., M.P.H., Study Chair, Associate Professor and physician at Fred Hutch and University of Washington, at the 5th International Workshop on CAR-T and Immunotherapies (iwCAR-T). The multicenter study data show clinical responses in four of four patients with relapsed or refractory indolent NHL at the starting dose of 3.3 x 106 CAR-T cells/kg, a dose comparable to that employed for the majority of the indolent lymphoma patients in the Fred Hutch trial.

The multicenter data also show persistence of CAR-T cells at 6+ months and favorable safety data with only Grade 1 cytokine release syndrome (CRS) reported to date. Two patients with follicular lymphoma had complete response (CR) by both PET-CT and bone marrow, one of whom had been previously treated with a CD19-directed CAR-T. A third patient, with a diagnosis of Waldenstrom macroglobulinemia (WM), who had nine prior treatments and high disease burden, achieved complete metabolic response by PET-CT, morphologic clearance of lymphoma in bone marrow, and resolution of the IgM monoclonal protein. The fourth patient, with a diagnosis of hairy cell leukemia variant, who had been heavily transfusion dependent, continues to have stable disease with decreased disease in his bone marrow and achieved complete transfusion independence, which is ongoing at 6+ months.

Following treatment of the four indolent NHL patients, the Safety Review Committee unanimously approved dose escalation to 1.0 x 107 CAR-T cells/kg. The five-center Phase 1/2 clinical trial is a three-arm study targeting CLL and B-NHL, including FL, diffuse large B-cell lymphoma and mantle cell lymphoma. We anticipate adding a sixth center by the end of 2023.

The Mustang-sponsored multicenter clinical trial is using the same lentiviral vector as the Fred Hutch-sponsored single-center trial. Included in the eligibility criteria are patients who have relapsed after treatment with CD19 CAR-T cell therapy. Additionally, the FL arm will evaluate other indolent histologies including Waldenstrom macroglobulinemia, a rare type of B-NHL for which the U.S. Food and Drug Administration granted MB-106 Orphan Drug Designation.

Patients will be enrolled in one of three arms, based on their primary diagnosis; escalating MB-106 dose levels will be tested independently in each arm using a 3+3 design. A total of up to 18 patients are anticipated to be treated in each Phase 1 arm, including six patients at the maximum tolerated dose in each independent arm. Safety of each dose level will be reviewed for each arm until the maximum tolerated dose has been reached and the recommended Phase 2 dose (RP2D) has been established for each arm.

An assessment of the safety and tolerability of the dose will be made by the Safety Review Committee based on the data from the 28-day dose-limiting toxicity observation period. In Phase 2, specific arms of relapsed or refractory CD20-positive B-cell hematologic malignancies will be treated with MB-106 at the respective RP2D for each arm. The two top priorities are WM and diffuse large B-cell lymphoma (DLBCL) relapsed from prior CD19 CAR-T therapy.

Each arm will initially include up to 20 patients. Based on the results of the interim analysis, up to an additional 51 patients may be added to each of the arms.