Takeda bags MD Anderson CAR-NKs, plans 2021 pivotal trial

Takeda US facility
Takeda plans to start a pivotal trial of the CD19 candidate in 2021. (Takeda)

Takeda has struck a deal with the MD Anderson Cancer Center to access CAR-NK cell therapies. The deal grants Takeda rights to up to four programs, including natural killer (NK) cell therapies aimed at CD19 and BCMA.

NK cells have some potential advantages over the T cells that have underpinned the first wave of oncology cell therapies. NK cells taken from one person can be transplanted into another individual without causing graft-versus-host disease, thereby resulting in a simpler, cheaper production process than is required for existing chimeric antigen receptor T cells (CAR-Ts). In addition, CAR-NKs look to be free from the severe cytokine release syndrome and neurotoxicity that dogged CAR-Ts. 

At MD Anderson, Katy Rezvani and her colleagues have worked to realize those potential benefits of NK cells, resulting in a platform that has spawned cell therapies against CD19 and BCMA. CD19 is the receptor targeted by first-generation CAR-Ts Kymriah and Yescarta, while BCMA is the focus of many groups working with several modalities, including cell therapies.

Takeda is forging into these competitive niches by securing the rights to MD Anderson’s CAR-NKs. The agreement gives Takeda exclusive rights to four assets, including the CD19 and BCMA candidates, and the chance to collaborate with MD Anderson on their development. Takeda plans to start a pivotal trial of the CD19 candidate in 2021. 

That target reflects the progress made so far. MD Anderson is already testing the CD19 cell therapy in patients with relapsed and refractory B-cell malignancies. Based on the profile seen in the phase 1/2a, Takeda thinks the CD19 candidate may be safe enough to dose in outpatient settings.

If the candidate proves to be a safer, cheaper cell therapy that can be dosed outside of hospitals it will have a shot at taking the modality into the mainstream. However, there are good reasons T cells, not NK cells, have dominated the early period of anti-cancer cell therapies. 

NK cells are found in low numbers in the body, meaning effective expansion technologies are needed to generate therapeutic doses. Also, NK cells have short half-lives, meaning they are cleared from the body before having the desired effect. MD Anderson’s CAR-NK production process features an in vitro expansion step and adds IL-15 to the cells to increase persistence and, by extension, efficacy. 

Takeda will now work to find out whether the platform can deliver a commercial CAR-NK cell therapy. The CAR-NK work will slot into a growing cell therapy pipeline at Takeda, which has struck deals to access gamma delta CAR-Ts, stem cell based CAR-Ts and anti-solid tumor CAR-Ts in recent years. 

Neither Takeda nor MD Anderson has disclosed the numbers tied to the CAR-NK deal, stating only that it features an upfront fee plus milestones and royalties tied to each program.