CAR-T rolls on

20.02.2018

Over recent months, the cellular immunotherapy landscape has continued to develop apace. Various new acquisitions and collaborations have been announced, as well as news of patient success stories from the many ongoing trials regularly hitting the headlines. As an update to the article featured on page 18 of our Biotech Review, we have picked out a few commercial highlights below:

In December 2017 Janssen announced a deal with with two Legend Biotech entities, both subsidiaries of the innovative Chinese biotech company Genscript Biotech Corporation, to develop, manufacture and commercialise Legend’s experimental CAR-T therapy LCAR-B38M. This therapy specifically targets the B-cell maturation antigen (BCMA) which is a protein highly expressed on myeloma cells. It is thought to have the potential to transform the treatment of multiple myeloma, a blood cancer which is incurable for many patients. Whilst Kite’s Yescarta and Novartis’ Kymriah have already been approved in the US, this is the first CAR-T therapy accepted for review by the Chinese FDA.

In January 2018 Kite announced that it had entered a clinical collaboration with Pfizer to investigate a combination of Kite’s CAR-T therapy, Yescarta, with Pfizer’s monoclonal antibody utomilumab in refractory large B-cell lymphoma. Yescarta is the first CAR-T cell therapy to be indicated for the treatment of adult patients with relapsed or refractory large B-cell lymphoma, while utomilumab, a fully humanised 4-1 BB agonist monoclonal antibody, has been shown in preclinical models to enhance T-cell-mediated immune responses. A multi-center Phase 1/2 study is expected to begin later in 2018 and the results to be used to evaluate options for further development of this or other of Kite’s T-cell products and utomilumab. This is an example of the use of CAR-T therapies in combination with monoclonal antibodies in order to maximise the potential of both.

As noted in the article above, it is not Pfizer’s first foray into the world of CAR-T. They are also in collaboration with Cellectis (a clinical stage French biopharma company) and Servier in relation to allogenic CAR-T therapies i.e. “off the shelf” CAR-T products which involve treating patients with genetically engineered T-cells from healthy donors, rather than autologous products such as Kite’s Yescarta and Novartis’ Kymriah which involve extracting T-cells from each patient and genetically engineering these. In January and February 2018, Cellectis was granted US patents which relate to methods by which T-cells are genetically modified using transient expression of CRISPR/Cas9 components (an equivalent European patent was granted in August 2017), such that the T-cells can then be used in cellular immunotherapies.

Also in January 2018 Celgene announced that it had agreed to acquire Juno Therapeutics for approximately $9 billion (in February 2018 Celgene announced that its wholly-owned subsidiary, Blue Magpie Corporation, had commenced the tender offer). Juno has long been a front-runner in CAR-T and other cell immunotherapies such as TCR (T cell receptor) therapies and has a broad portfolio evaluating multiple targets and cancer indications. The two companies entered into a strategic collaboration back in June 2015 in order to leverage their T cell capabilities in the CAR-T space and this has clearly been a success.

We look forward to seeing what the rest of 2018 will bring – watch this space.

Rachel Mumby

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Louisa Jacobs

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