Novartis aims for dominance in next generation immunotherapy

Novartis has today announced deals which it hopes will put it in the driving seat for the next generation of cancer immunotherapies.

The world’s biggest pharma company by revenue, Novartis is currently trailing far behind the leaders in the field, the PD-1 inhibitor drugs, Merck’s Keytruda and Bristol-Myers Squibb’s Opdivo.

The Swiss firm has today announced the acquisition of Massachusetts-based Admune Therapeutics, and new licensing agreements with Palobiofarma and XOMA to bolster its immuno-oncology pipeline.

Novartis has four candidates in clinical trials, and five more agents expected to enter the clinic by the end of 2016. This portfolio includes a wide range of immunotherapy mechanisms which stimulate the immune system to combat cancers: novel checkpoint inhibitors, chimeric antigen receptor T-cell (CART) technology, myeloid cell targeting agents, and STING agonists.

Novartis’ myeloid cell targeting programme (MCS-110) and checkpoint inhibitors targeting PD-1 (PDR001), LAG-3 (LAG525), are in phase I trials. The CART programme (CTL019) is in phase II. The anti-TIM-3 programme (MGB453) is expected to enter the clinic by the end of 2015 and a STING agonist (MIW815), through collaboration with Aduro Biotech, and GITR agonist are progressing towards first-in-human trials in 2016.

The Admune acquisition brings with it an IL-15 agonist currently in phase I trials for metastatic cancer, while the Palobiofarma deal gives Novartis rights to PBF-509, an adenosine receptor antagonist currently in phase I for non-small cell lung cancer.

The agreement with XOMA gives Novartis development and marketing rights to XOMA’s TGF-beta antibody programmes. All three programmes will be explored as monotherapies and as combination with Novartis’ immuno-oncology and targeted therapy portfolios.

“The first wave of immuno-oncology therapies has demonstrated the impact this approach can have in treating certain types of tumours,” said Mark Fishman, President of the Novartis Institutes for BioMedical Research. “To realise its full potential requires exploration of the complex system of biological pathways in the tumour microenvironment with agents that can stimulate the immune system to attack a wider variety of tumours.”

In pre-clinical studies, IL-15 therapies have been shown to activate CD8+, CD4+ memory T cells and Natural Killer (NK) cells that play a critical role in stimulating the immune system. Adenosine and TGFß both drive immune suppression in the tumour microenvironment, which allows cancer cells to escape immune surveillance, making inhibition of these two pathways an attractive next-generation immuno-oncology approach.

Novartis is far from alone in looking to lead the second wave of immunotherapy, however, with many firms investing heavily in the field. Pfizer and Germany’s Merck also have a broad alliance, led by anti-PD-L1 IgG1 monoclonal antibody avelumab. It received fast track designation from the US FDA earlier this month for metastatic Merkel cell carcinoma (MCC), a rare and aggressive type of skin cancer.

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