AZ signs three cancer immunotherapy deals

AstraZeneca’s partnering teams have been working on overdrive, signing three new projects in the hot area of immuno-oncology in a matter of days.

Today, AZ announced a strategic alliance with Innovio Pharmaceuticals that will give it rights to a cancer vaccine in phase I/II trials, with the two companies pledging to work together on several other vaccine candidates.

The lead project – INO-3112 – is a synthetic DNA vaccine that targets cancers caused by human papillomavirus (HPV) types 16 and 18, including cervical and head and neck cancers. It works by stimulating immune responses against tumour cells that express two antigens (called E6 and E7).

The vaccine consists of an immune therapy called VGX-3100 that has already shown activity in a phase II trial in HPV-related cancer and pre-cancerous states, as well as a DNA plasmid coding for the immune-boosting cytokine interleukin-12 (IL-12) codenamed INO-9012.

It is administered using an electroporation device, which applies an electrical charge across the skin to increase its permeability and help the vaccine components be absorbed.

AZ’s MedImmune subsidiary will study INO-3112 in combination with its own pipeline of immuno-oncology compounds currently headed by PD-L1 inhibitor durvalumab (MEDI4736) which is playing catch-up with Bristol-Myers Squibb’s Opdivo (nivolumab) and Merck & Co’s Keytruda (pembrolizumab), both already on the market.

The vaccine is also due to start a phase II trial shortly in patients with locally-advanced cervical cancer.

The agreement with Inovio – which includes $27.5 million in upfront fees and development and commercial milestone payments of up to $700 million – comes shortly after AZ announced two other deals with Heptares and Mirati Therapeutics as it continues to add to its cancer immunotherapy pipeline.

MedImmune has licensed exclusive rights to Heptares’ adenosine A2A receptor antagonist HTL-2071, a small-molecule drug that is thought to promote the anticancer activity of T lymphocytes.

The two firms will once again look at combining HTL-2071 with MedImmune’s immuno-oncology pipeline and will also collaborate on the discovery of other A2A blocking compounds. Heptares stands to receive an upfront payment of $10 million under the terms of the deal along with up to $500 million in milestones.

The agreement with Mirati focuses on testing durvalumab alongside mocetinostat, a histone deacetylase inhibitor in the same class as already-approved drugs including Merck & Co’s Zolinza (vorinostat), Novartis’ Farydak (panobinostat) and Spectrum Pharmaceuticals’ Beleodaq (belinostat).

AZ and Mitari said they will test the combination initially in non-small cell lung cancer (NSCLC), with trials due to kick off next year. Additional cancers may be added to the programme in future, according to the two companies.

The market for immuno-oncology therapies could climb as high as $33 billion in 2022, according to Morningstar analysts, who describe the drugs as heralding a “paradigm shift” in cancer treatment.

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