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Leveraging 3D antigen design approach, we designed antigens and immunized rodents in order to derive new antibodies that exclusively block the epitope binding surface of Programmed cell death protein 1, (PD1 also known as CD279), from its ligands PD-L1 and PD-L2. We focus on antibody candidates that exclusively block this binding surface domain and do not block adjacent domains.
In late 2014, two PD1 antibodies were approved in the U.S. for the first time for clinical treatment of late stage melanoma. In 2015 these antibodies were approved also to treat certain stages of lung cancer. Revenues from these two product sales are expected to exceed $1.0 billion in 2015. Recently, clinical results of a combination treatment of PD1 antibody and CTLA-4 antibody showed a strong synergy in the treatment of late stage melanoma, both as a first line therapy and as a second line treatment. Accordingly, the combination treatment of PD1 antibody with CTLA-4 antibody was approved in the U.S. to treat late stage melanoma.
PD1 is a cell surface receptor that belongs to the immunoglobulin superfamily and is expressed on T cells, B cells, and macrophages. By interacting with its ligands PDL1 and PDL2 it down regulates the immune system by preventing the activation of T-cells, which in turn reduces autoimmunity and promotes self-tolerance.
We plan to initially focus our pre clinical trials with models that address melanoma diseases and lung cancer, alone and in combination treatment with CTLA-4 antibody.