Date: 2015-01-21
Type of information: R&D agreement
Compound: immunotherapy and tumor targeted therapies including MEDI4736 (PD-L1), MEDI0680 (PD-1), tremelimumab (CTLA-4) and MEDI6469 (mOX40)
Company: MedImmune (USA - global biologics arm of AstraZeneca (UK) National Cancer Institute (USA)
Therapeutic area: Cancer - Oncology
Type agreement: R&D
Action mechanism: monoclonal antibody/immune checkpoint inhibitor. MEDI4736 is a 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.This antibody is directed against B7-H1, have been shown to block the interaction between B7-H1 and its receptors, PD-1 and CD80 (B7-1). This blockade may help to overcome the immunosuppressive effects of B7-H1 on anti-tumor T cells. Last May, AstraZeneca has announced the start of a Phase III programme for MEDI4736 for the treatment of non-small cell lung cancer (NSCLC). MEDI0680 is a human monoclonal antibody directed against programmed cell death protein 1 ( PD-1). It blocks PD-1, a protein on T cells that limits their activity when it is bound by PD-L1 or PD-L2 Tremelimumab is a fully human monoclonal antibody which binds to the protein CTLA-4, expressed on the surface of activated T lymphocytes. MEDI6469 (mOX40) is a murine anti-OX40 monoclonal antibody. The OX40 receptor is a member of the tumor necrosis factor (TNF) receptor superfamily expressed on the surface of activated T-cells.
Disease:
Details: * On January 21, 2015, MedImmune, the global biologics research and development arm of AstraZeneca, announced that it has entered into two umbrella Cooperative Research and Development Agreements (CRADAs) with the National Cancer Institute (NCI), a part of the National Institutes of Health (NIH), that are focused on immunotherapy and tumor targeted therapies for cancer.
These agreements will leverage technological know-how and resources from each organization to support preclinical and clinical research and development activities in these areas. MedImmune will gain access to NCI’s unique preclinical and clinical expertise to be applied to biological understanding of MedImmune’s immunomodulatory and tumor-targeted investigational antibody drugs with the goal of translating preclinical research to the clinic.
Four initial preclinical research projects have been identified. Two will investigate the combination of immunotherapy agents in novel mouse models that better represent human tumors and two projects will evaluate antibodies that specifically attack tumor cells to evaluate molecular imaging of antibody drug conjugates and evaluate the therapeutic efficacy of cancer stem cells. Using immunotherapy candidates provided by MedImmune, the two immunotherapy projects will evaluate:
Combination activity of four investigational compounds in genetically engineered mouse models; MEDI4736 (PD-L1), MEDI0680 (PD-1), tremelimumab (CTLA-4) and MEDI6469 (mOX40)
Cancer vaccine combinations with three investigational agents in preclinical models; MEDI4736, tremelimumab and MEDI6469 (mOX40)
The second area of research under this partnership, tumor targeted therapies for cancer, will use cutting-edge technology such as antibody drug conjugates and anti-cancer stem cell therapies to directly and specifically attack tumor cells. The work will evaluate molecular imaging for MedImmune’s antibody drug conjugates and their therapeutic efficacy in cancer stem cell models.
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