Mustang Bio & City of Hope Announce First Patient Dosed in Phase 1 Clinical Trial

Mustang Bio, Inc. and City of Hope recently announced the first patient has been dosed in a clinical trial to establish the safety and feasibility of administering MB-101 (autologous IL13Rα2-CAR T cells) to patients with leptomeningeal brain tumors (eg, glioblastoma, ependymoma, or medulloblastoma). The trial will enroll up to 30 patients and is taking place at City of Hope, where this chimeric antigen receptor T (CAR T) cell therapy was initially developed. Even though it is a single center clinical trial, Mustang and City of Hope will facilitate patient transfers from other centers, as needed.

All subjects enrolled in the Phase 1 single-center, two-arm clinical trial will undergo surgery for the placement of an intraventricular (ICV) Rickham catheter for CAR T cell delivery. The Phase 1 trial will determine the safety and feasibility of administering MB-101 through the ICV Rickham catheter over four weekly cycles in patients with glioblastoma (Arm 1) and ependymoma or medulloblastoma (Arm 2). The primary endpoints that will be evaluated are toxicity and survival at three months. Secondary endpoints include overall survival, CAR T and endogenous T cell levels, cytokine levels and phenotype detection in peripheral blood, tumor cyst fluid and cerebrospinal fluid.

Lisa Feldman, MD, PhD, a neurosurgeon and Assistant Clinical Professor in the Division of Neurosurgery at City of Hope and principal investigator of the clinical trial, commented, “Based on our research to date, including a previous clinical trial at City of Hope, further evaluation is warranted for this CAR T cell therapy. The prior clinical trial demonstrated encouraging potential of administering autologous IL13Rα2-CAR T cells intraventricularly to help treat patients with leptomeningeal brain tumors, a form of metastatic brain cancer that is difficult to treat. We continue to work closely with the Mustang team to potentially bring a safe, effective treatment option to patients suffering with this life-threatening disease.”

Manuel Litchman, MD, President and Chief Executive Officer of Mustang, added “The successful dosing of the first patient in this clinical trial of MB-101 is an important milestone in Mustang’s development program. We are pleased to support City of Hope to further study MB-101 in leptomeningeal brain tumors to potentially bring hope to patients suffering from this devastating and fatal disease. MB-101 has already demonstrated therapeutic potential when infused into the ventricular system, including delivering a complete response in a patient with leptomeningeal glioblastoma that was published in the New England Journal of Medicine. We aim to generate additional data that supports the advancement of this program.”

Additional information about the trial can be found on clinicaltrials.gov using the identifier NCT04661384.

IL13Rα2 is an attractive target for CAR T therapy as it has limited expression in normal tissue but is overexpressed on the surface of the majority of malignant glioma cells, including glioblastoma multiforme, ependymoma and medulloblastoma. CAR T cells are designed to express a membrane‐tethered IL‐13 receptor ligand (IL‐13) incorporating a single‐point mutation that provides high affinity for IL13Rα2 and reduces binding to IL13Rα1 in order to reduce healthy tissue targeting. Mustang is developing MB‐101 as an optimized CAR T product incorporating enhancements in CAR design and T cell engineering to improve antitumor potency and T cell persistence. MB‐101 includes a second‐generation hinge optimized CAR containing mutations in the IgG4 linker to reduce off‐target Fc interactions, the 4-1BB (CD137) co‐stimulatory signaling domain for improved persistence of CAR T cells and the extracellular domain of CD19 as a selection/safety marker. To further improve persistence, central memory T cells are enriched and genetically engineered using a manufacturing process that limits ex vivo expansion to reduce T cell exhaustion and maintain a memory T cell phenotype.

Mustang Bio, Inc. is a clinical-stage biopharmaceutical company focused on translating today’s medical breakthroughs in cell and gene therapies into potential cures for hematologic cancers, solid tumors and rare genetic diseases. Mustang aims to acquire rights to these technologies by licensing or otherwise acquiring an ownership interest, to fund research and development and to outlicense or bring the technologies to market. Mustang has partnered with top medical institutions to advance the development of CAR T therapies across multiple cancers, as well as a lentiviral gene therapy for X-linked severe combined immunodeficiency (XSCID), also known as bubble boy disease. Mustang is registered under the Securities Exchange Act of 1934, as amended, and files periodic reports with the U.S. Securities and Exchange Commission (“SEC”). Mustang was founded by Fortress Biotech, Inc. (NASDAQ: FBIO). For more information, visit mustangbio.com.

City of Hope is an independent biomedical research and treatment center for cancer, diabetes and other life-threatening diseases. Founded in 1913, City of Hope is a leader in bone marrow transplantation and immunotherapy such as CAR T cell therapy. City of Hope’s translational research and personalized treatment protocols advance care throughout the world. Human synthetic insulin, monoclonal antibodies, and numerous breakthrough cancer drugs are based on technology developed at the institution.  Translational Genomics Research Institute (TGen) became a part of City of Hope in 2016. AccessHope, a wholly owned subsidiary, was launched in 2019, dedicated to serving employers and their health care partners by providing access to City of Hope’s exceptional cancer expertise. A National Cancer Institute-designated comprehensive cancer center and a founding member of the National Comprehensive Cancer Network, City of Hope is ranked among the nation’s Best Hospitals in cancer by US News & World Report. Its main campus is located near Los Angeles, with additional locations throughout Southern California and in Arizona. For more information about City of Hope, follow us on Facebook, Twitter, YouTube or Instagram.