On November 5, 2019 The University of Texas MD Anderson Cancer Center and Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) ("Takeda") reported an exclusive license agreement and research agreement to develop cord blood-derived chimeric antigen receptor-directed natural killer (CAR NK)-cell therapies, ‘armored’ with IL-15, for the treatment of B-cell malignancies and other cancers (Press release, Takeda, NOV 5, 2019, View Source [SID1234550313]).

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Under the agreement, Takeda will receive access to MD Anderson’s CAR NK platform and the exclusive rights to develop and commercialize up to four programs, including a CD19-targeted CAR NK-cell therapy and a B-cell maturation antigen (BCMA)-targeted CAR NK-cell therapy. Takeda and MD Anderson will also conduct a research collaboration to further develop these CAR NK programs.

"Our vision is to improve upon existing treatments by developing armored CAR NKs that could be administered off-the-shelf in an outpatient setting—enabling more patients to be treated effectively, quickly and with minimal toxicities," said Katy Rezvani, M.D., Ph.D., professor of Stem Cell Transplantation and Cellular Therapy at MD Anderson. "With their expertise in hematologic malignancies and commitment to developing next-generation cell therapies, Takeda is the ideal collaborator to help our team advance CAR NK-cell therapies to patients in need of treatments."

A Novel Approach to Delivering Off-the-Shelf CARs in an Outpatient Setting
MD Anderson’s allogeneic CAR NK platform isolates NK cells from umbilical cord blood and engineers them to express CARs against specified cancer targets. CAR NK cells are modified with a retroviral vector to deliver genes and enhance their effectiveness to attack specific tumors. A CD19 CAR increases the cells’ specificity for B-cell malignancies while the immunocytokine IL-15 enhances the proliferation and survival of the CAR NK cells in the body.

In contrast to current CAR T-cell therapies that utilize a patient’s own genetically modified T-cells and require a multi-week manufacturing process, CAR NK cells are intended to be manufactured from a non-related donor source and stored for off-the-shelf use, allowing treatment to be delivered more rapidly.

It is anticipated that the CD19 CAR NK-cell therapy could be administered in an outpatient setting. In an ongoing phase 1/2a clinical study treating patients with relapsed and refractory B-cell malignances, the CD19 CAR NK-cell therapy has not been associated with the severe cytokine release syndrome (CRS) or neurotoxicity observed with existing CAR-T therapies.

The development of MD Anderson’s CAR NK platform is led by Dr. Rezvani and is further supported by the adoptive cell therapy platform, Chronic Lymphocytic Leukemia Moon Shot and B-Cell Lymphoma Moon Shot, all part of the institution’s Moon Shots Program, a collaborative effort to rapidly develop scientific discoveries into meaningful clinical advances that save patients’ lives.

Takeda: Accelerating the Development of Multiple Next-Generation CAR Platforms
"MD Anderson’s CAR NK platform represents the curative potential of cell therapies, which is why we are establishing the CD19 CAR NK as our lead cell therapy candidate in oncology," said Andy Plump, M.D., Ph.D., President of Research and Development at Takeda. "We need to work swiftly and with purpose, and as such, we intend to initiate a pivotal study of the CD19 CAR NK in 2021."

In addition to CAR NK-cell therapies, Takeda and its partners are investigating multiple approaches to improving the safety, efficacy and accessibility of first-generation CAR T-cell therapies including gamma delta CAR Ts, induced pluripotent stem cell-derived CAR Ts, CAR Ts targeting solid tumors, and other next-generation approaches. Takeda plans to advance five oncology cell therapies to the clinic by the end of FY20.1 These platforms are being developed both with partners and by applying the expertise of Takeda’s translational cell therapy engine which provides bioengineering, chemistry, manufacturing and control (CMC), clinical and translational capabilities in a single footprint to overcome many of the manufacturing challenges experienced in cell therapy development.

Takeda is responsible for the development, manufacturing and commercialization of CAR NK products resulting under the agreement. MD Anderson will receive an upfront payment and is eligible to receive development and commercial milestones for each target as well as tiered royalties on net sales of any such CAR NK product.

MD Anderson and Takeda will continue research for the additional targets and CAR NK platform under the direction of a joint research committee. MD Anderson will implement an Institutional Conflict of Interest Management and Monitoring Plan for this research.