In March of 2015 HaemaLogiX acquired all the assets of Immune System Therapeutics (IST) including their lead drug called MDX-1097 or IST-1097, (now named KappaMab). This is an antibody, (a large protein) in a new class of medicines that is being developed for initial use in the treatment of a fatal form of cancer known as multiple myeloma or plasma cell myeloma. Myeloma is a cancer of the plasma cells which accumulate in the bone marrow. KappaMab targets the malignant plasma cells which are a form of B-cell and are responsible for the progression of the disease.
The malignant plasma cells produce a protein on the surface of the cell and this protein has been identified as Kappa Myeloma Antigen (KMA). KMA has not been found on normal plasma cells or B-cells nor on any normal human tissue and it is believed to be a marker for the abnormal cell. The antibody, KappaMab, was created to specifically bind to KMA and target the malignant plasma cells that are present in the bone marrow of myeloma patients. When the antibody attaches to KMA, effector cells from the patient's own immune system recognize that the myeloma cell is tagged and should be destroyed. This is a normal defense mechanism of the immune system and is called antibody dependent cellular cytotoxicity (ADCC) whereby the antibody induces or activates the immune system to attack the antibody tagged cells.
Myeloma is a clonal disease, in other words all the malignant plasma cells in the bone marrow have developed from a single parent cell. The parent cell can be either kappa-type which have KMA on their cell surface or lambda-type which have LMA (lambda myeloma antigen) on the cell surface. In general two thirds (~70%) of myeloma patients have KMA and one third (~30%) have LMA. HaemaLogiX has acquired antibodies, named LambdaMab, which specifically target the form of myeloma that expresses LMA and these antibodies are in preclinical development for the treatment of myeloma and in particular a rare form of myeloma called POEMS 1 syndrome whereby almost all patients have lambda-type disease.
The Haemalogix antibodies, KappaMab and LambdaMab, have been shown to specifically target the cell surface proteins KMA and LMA respectively that are found on abnormal plasma cells and have not been shown on the surface of normal plasma cells or B cells. Two types of Chimeric Antigen Receptor-T cells (CAR-T cells) can be created from these antibodies and these have been called KMA.CAR-T cell and LMA.CAR-T cell. The KMA.CAR-T cell is currently in preclinical development and will be tested in nonclinical studies before entering the clinic to treat patients with myeloma. A similar approach will be taken for the development of the LMA.CAR-T cell.