Pipeline
A Unique Pipeline Created from BRITE and HIO Screening Platforms
Humoral Immuno-Oncology (HIO) mechanisms utilize antibodies as well as immune effector cells to kill dysregulated cancer cells. Some tumor cells produce immunosuppressive factors (HIO factors) that reduce HIO activity of therapeutic antibodies such as Rituxan® and Herceptin®.
Our Block-Removed Immunoglobulin Technology (BRITE) and HIO screening platforms allowed us to develop a unique pipeline of HIO factor-refractory therapeutic agents, HIO factor antagonist, or activator of immune-effector cells including natural killer (NK) cells.
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NAV-001
NAV-001 is a next-generation antibody-drug conjugate (ADC). NAV-001 targets and kills tumor cells that express mesothelin (MSLN) via release of its toxic payload (figure). We have discovered that HIO-1 (CA125) produced in the tumor microenvironment can diminish payload delivery inside the tumor cells. With this knowledge, we used our proprietary screening platforms to select an ADC that is refractory to HIO-1 and is more effective at killing MSLN-positive tumor cells. NAV-001 is being developed for advanced stage lung adenocarcinoma (mesothelin overexpressed in 54% of cases) and first-line mesothelioma (mesothelin over-expressed in 100% of epithelioid mesothelioma).
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NAV-006
NAV-006 is a next-generation rituximab. We have discovered that rituximab is bound and immunosuppressed by HIO-1 (CA125) produced in the tumor microenvironment. With this knowledge, we generated NAV-006 by using our Block-Removed Immunoglobulin Technology or BRITE. The BRITE enhancement removes the HIO-1 (CA125) binding site so that NAV-006 is more effective than rituximab at killing lymphoma cells. NAV-006 is being developed for treating HIO-1-positive Non-Hodgkin’s Lymphoma.
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NAV-201
NAV-201 is a small-molecule compound that binds to CD16/Fc Receptor and activates NK cells, which go on to kill tumor cells (figure). NAV-201 can restore NK cell activity in the presence of immunosuppressive HIO factors. NAV-201 has been identified from a library of natural compounds by using our proprietary BRITE screening platforms and has been enhanced by structure-activity relationship analyses. NAV-201 is being developed for treating cancers immunosuppressed by HIO factors.
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NAV-004
NAV-004 is a next-generation immunotoxin with improved immunogenic profile. This novel de-immunized immunotoxin specifically targets and kills regulatory T cell (T reg) via engagement of their CD25 receptors. By this mode of action, NAV-004 can remove T cell-suppressing factors produced by T regs from the tumor microenvironment, allowing re-activation of effector immune cells and restoration of their tumor-killing activity.
