Astellas partners with Adaptimmune in latest move into cell therapy

The companies will work to develop allogeneic CAR-T and T-cell receptor therapies. Astellas has made multiple moves into cell and gene therapy in the past month.

Although the two CAR-T cell therapies that the Food and Drug Administration approved in 2017 remain the only ones on the market, a number of companies have busied themselves with their own programs, developing their own capabilities and also partnering with other companies. The latest such deal happened amid the J.P. Morgan Healthcare Conference in San Francisco as a large Japanese drugmaker partnered with a company developing cell therapies.

Tokyo-based Astellas Pharma and Adaptimmune, based in Philadelphia and Oxfordshire, U.K., said Tuesday that they will pick three molecular targets and develop T cell-based therapies directed at them, though they will not be targets that Adaptimmune is already developing in-house or with other partners. The companies will develop CAR-T as well as T-cell receptor (TCR) therapies, particularly “off-the-shelf” allogeneic CAR-Ts and T-cell receptors that can target cancer cells independently of their human leukocyte antigen profile. Under the deal, Astellas will pay $50 million upfront to Adaptimmune, together with milestone payments worth up to $897 million in milestones.

Most TCRs that have been developed are HLA-restricted, meaning they can only be used in patients with particular genetic profiles. Meanwhile, both FDA-approved CAR-Ts, Novartis’ Kymriah (tisagenlecleucel) and Gilead Sciences’ Yescarta (axicabtagene ciloleucel), are autologous, meaning they’re made from patient’s own T cells; allogeneic CAR-Ts are made from donor cells.

The deal is only the latest foray by Astellas into cell and gene therapy in the past month. At the beginning of December, it announced it would buy gene therapy maker Audentes Therapeutics for $3 billion, a deal that it completed on Wednesday. And at the end of December, it made a deal to buy Xyphos – and its cell therapy development platform – for $665 million.

Along with the two approved CAR-T therapies, the next two most likely to win approval – Bristol-Myers Squibb’s lisocabtagene maraleucel and BMS and bluebird bio’s idecabtagene vicleucel – are also autologous. However, allogeneic CAR-Ts have attracted significant attention from drugmakers and investors as well, given their potential to be used in those patients for whom autologous CAR-Ts are unsuitable.

A prominent company involved in allogeneic CAR-Ts is Allogene Therapeutics, which has product candidates in Phase I development for acute lymphoblastic leukemia, non-Hodgkin’s lymphoma and multiple myeloma. Its lead candidate, UCART19, is being developed under a joint clinical collaboration with French drugmaker Servier. On Monday, Allogene said it would partner with Springworks Therapeutics to combine ALLO-715, its CAR-T for multiple myeloma, with Springworks’ drug nirogacestat, a drug that has been shown in preclinical models to increase cell-surface density of BCMA, the antigen ALLO-715 targets, thereby potentially boosting the CAR-T’s efficacy.

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