AstraZeneca and its global biologics research and development arm, MedImmune, have signed a co-development and commercialization agreement with Innate Pharma SA to accelerate and broaden the development of Innate Pharma's proprietary anti-NKG2A antibody, IPH2201, including in combination with MEDI4736, an anti-PD-L1 immune checkpoint inhibitor developed by MedImmune.

Currently in phase II development, IPH2201 is a potential first-in-class humanised IgG4 antibody. NKG2A is a checkpoint receptor that inhibits the anti-cancer functions of Natural Killer (NK) and cytotoxic T-cells.

The initial development plan includes phase II combination clinical trials with MEDI4736 in solid tumours; multiple phase II trials planned by Innate to study IPH2201 both as monotherapy and in combination with currently approved treatments across a range of cancers; and the development of associated biomarkers.

The combination of IPH2201 with MEDI4736 adds to the broad programme of immuno-oncology combination trials that AstraZeneca and MedImmune have planned and underway. The studies aim to address multiple immune pathways, harnessing AstraZeneca’s own extensive pipeline and working in partnership to explore the significant potential of immunotherapies in transforming the way cancer patients are treated.

Under the terms of the agreements, AstraZeneca will make an initial payment to Innate of USD 250 million, which includes the consideration for exclusive global rights to co-develop and commercialise IPH2201 in combination with MEDI4736, as well as access to IPH2201 in monotherapy and other combinations in certain treatment areas.

AstraZeneca will pay a further USD100 million prior to initiation of phase III development, as well as additional regulatory and sales-related milestones. AstraZeneca will book all sales and will pay Innate double-digit royalties on net sales. The arrangement includes the right for Innate to co-promote in Europe for a 50 per cent profit share in the territory.

Pascal Soriot, chief executive officer of AstraZeneca, said “We are pleased to collaborate with Innate Pharma to bring this prospective first-in-class treatment to cancer patients, further strengthening our broad immuno-oncology pipeline. We believe that combination therapy in immuno-oncology has the potential to be one of the most effective ways of treating cancer and that by targeting both innate and acquired immunity we have the opportunity to deliver important clinical benefit to patients across a range of cancers.”

Hervé Brailly, chief executive officer and co-founder of Innate Pharma, said “This agreement allows Innate Pharma to broaden and accelerate the development of anti-NKG2A while preserving our innovative development plan. It provides Innate Pharma with the capabilities and resources to transform the company towards late stage development and potential commercial stage with co-promotion rights. We look forward to partnering with AstraZeneca and MedImmune, leaders in immuno–oncology, in this transforming transaction for Innate Pharma.”

The transaction is subject to customary terms and conditions, including the expiration or termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act, and is expected to become effective in the second quarter of 2015.

IPH2201 is a first-in-class immune checkpoint inhibitor targeting NKG2A receptors expressed on tumour infiltrating cytotoxic NK and CD8 T lymphocytes.

NKG2A is an inhibitory receptor binding HLA-E. By expressing HLA-E, cancer cells can protect themselves from killing by NKG2A+ immune cells. HLA-E is frequently up-regulated on cancer cells of many solid tumours or haematological malignancies. IPH2201, a humanized IgG4, blocks the binding of NKG2A to HLA-E allowing activation of NK and cytotoxic T cell responses. Hence, IPH2201 may re-establish a broad anti-tumour response mediated by NK and T cells. IPH2201 may also enhance the cytotoxic potential of other therapeutic antibodies.
MEDI4736 is an investigational human monoclonal antibody directed against programmed cell death ligand 1 (PD-L1). Signals from PD-L1 help tumours avoid detection by the immune system. MEDI4736 blocks these signals, countering the tumour’s immune-evading tactics.

MEDI4736 was accelerated into phase III clinical development in non-small cell lung cancer and head and neck cancer. The OCEANS clinical development programme will evaluate MEDI4736 as monotherapy and in combination with a CTLA-4 (tremelimumab) in lung cancer, across the spectrum of the disease. In head and neck cancer, MEDI4736 is being investigated both as monotherapy and in combination with tremelimumab, looking at patients with different PD-L1 expression status who have failed on chemotherapy.

Innate Pharma S.A. is a biopharmaceutical company discovering and developing first-in-class therapeutic antibodies for the treatment of cancer and inflammatory diseases.