Thursday, August 17, 2023
Mustang Bio, Inc. (Nasdaq: MBIO), a clinical-stage biopharmaceutical company dedicated to harnessing the latest advancements in cell and gene therapies for potential treatments of challenging cancers and rare genetic disorders, has unveiled the initial findings from their ongoing Phase 1/2 multicenter clinical trial evaluating MB-106. MB-106 is a pioneering CD20-targeted autologous CAR-T cell therapy designed to address relapsed or refractory B-cell non-Hodgkin lymphomas (B-NHL) and chronic lymphocytic leukemia (CLL). These findings demonstrate promising clinical responses and affirm the treatment's safety and efficacy, consistent with the ongoing Phase 1/2 trial conducted at the Fred Hutchinson Cancer Center (Fred Hutch).
The primary data were presented by Dr. Mazyar Shadman, who serves as the Study Chair, Associate Professor, and physician at Fred Hutch and the University of Washington. The presentation took place at the 5th International Workshop on CAR-T and Immunotherapies (iwCAR-T).
Dr. Manuel Litchman, CEO of Mustang, expressed optimism regarding the initial results. He highlighted the clinical responses observed and the alignment of the trial's progress with that of the ongoing Fred Hutch trial. He noted that MB-106 exhibited a favorable safety profile and significant efficacy, outperforming currently approved autologous CAR-T therapies. He also mentioned that additional updates, including response data and dose escalation details, are expected to be presented at a major medical conference later this year.
The multicenter trial reported positive clinical responses in all four patients with relapsed or refractory indolent NHL at the initial dose of 3.3 x 106 CAR-T cells/kg. This dose mirrored that used for the majority of indolent lymphoma patients in the Fred Hutch trial. The data also indicated the persistence of CAR-T cells beyond six months and favorable safety data, with only Grade 1 cytokine release syndrome reported thus far.
Among the results, two patients with follicular lymphoma achieved complete response (CR) based on PET-CT and bone marrow evaluations. Notably, one of these patients had previously undergone treatment with a CD19-directed CAR-T therapy. Another patient diagnosed with Waldenstrom macroglobulinemia (WM) and a history of nine prior treatments achieved a complete metabolic response based on PET-CT, significant clearance of lymphoma in the bone marrow, and resolution of the IgM monoclonal protein. The fourth patient, diagnosed with a variant of hairy cell leukemia and heavily dependent on transfusions, experienced stable disease with reduced bone marrow disease and achieved complete transfusion independence at over six months.
Following the successful treatment of these indolent NHL patients, the Safety Review Committee unanimously approved a dose escalation to 1.0 x 107 CAR-T cells/kg.
Dr. Shadman emphasized the potential of MB-106 across various hematologic malignancies, including cases where patients had previously undergone CD19-directed CAR-T therapy. He highlighted that the initial data from the expanded evaluation are consistent with the safety profile observed in the ongoing Phase 1/2 trial at Fred Hutch. He also noted that the ongoing clinical trial data from Fred Hutch continued to demonstrate a high rate of complete and sustained responses.
Dr. Shadman also presented data from the ongoing Fred Hutch Phase 1/2 clinical trial, specifically in two B-NHL cohorts: follicular lymphoma (FL) and WM. In the FL cohort (n=20), an impressive overall response rate (ORR) of 95% was observed, with 80% achieving CR and 15% achieving a partial response. Notably, patients who achieved CR included one who had undergone prior CD19-directed CAR-T therapy. Among the six patients who experienced cytokine release syndrome, only one reached Grade 2. Several patients maintained CR for extended periods, with some exceeding two years, and one patient sustaining CR for over three years.
In the WM cohort (n=6), all of whom had received prior Bruton tyrosine kinase inhibitors, two patients achieved CR, with one maintaining CR beyond 22 months. No patients experienced severe cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome beyond Grade 2. None of the six WM patients required new therapy for their disease.
As previously communicated, Mustang intends to address WM patients in the Phase 1 segment of its multicenter clinical trial, a strategy aimed at facilitating a streamlined Phase 2 pathway for regulatory approval. The company has already secured Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) for WM. Importantly, there is currently no FDA-approved CAR-T cell therapy for WM. The pivotal Phase 2 WM trial is set to commence treatment of the first patient around mid-2024, potentially yielding top-line data by mid-2026. An end-of-Phase 1 meeting with the FDA is slated for the end of 2023 to solidify this strategic direction. Additionally, Mustang intends to request regenerative medicine advanced therapy (RMAT) designation for WM from the FDA in 2024. The data from the Fred Hutch clinical trial further underscore MB-106's potential for outpatient administration and its capacity to emerge as a leading immunotherapy option for patients previously treated with CD19-directed CAR-T cell therapy.
