Annual Report 2015
Engineering the Medicines
of Tomorrow

Nearly one million people
worldwide were
diagnosed with blood
cancer in 2015.

our research: fighting blood cancer

Antibodies attack
blood cancer cells in
a targeted manner.

our antibody mor208: mode of action

New developments
in the treatment
of blood cancer benefiting
patients.

the mor208 antibody in clinical development

What is blood cancer?

MorphoSys is involved in several cancer-related projects focused on the treatment of hematological cancers. These are cancers caused by pathologic hematopoiesis and commonly referred to as blood cancer.

In contrast to solid tumors that are initially limited to certain organs such as the breast, lungs or colon, hematological malignancies invade the entire body right from the start. This poses a particular challenge for the development of effective novel drugs.

Leukemias, lymphomas, myelomas – what types of blood cancer exist?

Blood cells are continuously produced from bone marrow and mature over the course of several intermediate steps within a complex process. Because these cells can become malignant and form blood cancer cells at different points in their development, this creates a very diverse group of hematological cancers requiring different targeted therapies.

MorphoSys is currently focused on the three blood cancer indications: diffuse large B cell lymphoma (DLBCLDLBCL: diffuse large B cell lymphoma, a subform of NHL), chronic lymphocytic leukemia (CLLCLL: Chronic lymphocytic leukemia; most common type of cancer of the blood and bone marrow, affecting the B cells) and multiple myelomamultiple myeloma: Type of cancer that develops in a subset of white blood cells called plasma cells formed in the bone marrow (MMMM: Multiple myeloma, type of cancer that develops in a subset of white blood cells called plasma cells formed in the bone marrow).

  1. Blood Formation (Hematopoiesis)

  2. Leukemia – “white blood”
  3. Lymphoma – lymphatic cancer
  4. DLBCL
  5. CLL
  6. MM
  1. Hematopoiesis is the formation of blood cellular components from hematopoietic stem cells in the bone marrow. Besides red blood cells (erythrocytes) and platelets (thrombocytes), the most diversified group of blood cells are the white blood cells (leukocytes). An important leukocyte subgroup are the cells of the lymphatic system (lymphocytes) comprising NK cellsNK cells: Natural killer cells of the body’s immune system; cells capable of recognizing and killing abnormal cells, e.g. tumor cells, T cellsT cells: An abbreviation for T-lymphocytes; a subtype of white blood cells that together with B-lymphocytes are responsible for the body’s immune defense, B cells, and plasma cells.

  2. Leukemia is Greek for “white blood.” Because of a malfunction, an excessive amount of malignant, and thus dysfunctional, white blood cells (leukocytes) is formed and released into the blood. They displace healthy blood cells and disturb the immune defense, transportation of oxygen and blood clotting. A characteristic of leukemia is the presence of tumor cells in the bloodstream.

    A distinction is made between acute leukemia and chronic leukemia. While acute leukemia can develop into a life-threatening disease within just a few weeks or months, chronic leukemia often spreads insidiously and unnoticed in patients for some time.

  3. Lymphomas are cancers of the lymphatic system.

    Everyone is familiar with the lymph system from the swollen lymph nodes that appear with a common cold. The lymph system is an important part of the human body’s emergency warning system – the “police force” of the immune system: White blood cells, called lymphocytes, are formed in the spleen, bone marrow and lymph nodes: T lymphocytes (T cells) recognize pathogens such as viruses and bacteria. B lymphocytes (B cells) produce the body’s own antibodies, which are used to combat these invaders.

    Lymphomas are characterized by degenerating and proliferating lymph cells (for example, B cells) displacing the healthy cells of hematopoiesis. The white blood cells no longer function, and the body’s defenses are weakened. This leads to tissue neoplasms such as excessively enlarged lymph nodes. There are two types of lymphomas: Hodgkin’s lymphoma and non-Hodgkin’s lymphomas. The latter group of diseases include the indication of diffuse large B cell lymphoma (DLBCL).

  4. Diffuse large B cell lymphoma (DLBCL) is the most common type of non-Hodgkin’s lymphoma in adults and represents about 30 % of all cases of non-Hodgkin’s lymphoma. Although this disease is prevalent mainly in the elderly, it can occur at any age. If left untreated, this aggressive disease that occurs within the B cells of the immune system can rapidly lead to death.

    There are only limited treatment options available for DLBCL. MorphoSys’s antibody MOR208 is currently in clinical development in this indication.

  5. In the case of chronic lymphocytic leukemia (CLL), B lymphocytes (B cells) of the body’s own immune system become malignant. These tumorous cells can no longer fight pathogens, and go on to multiply uncontrollably in the blood. The leukemia cells displace the still functional B lymphocytes and other blood cells, which are formed in the bone marrow. This creates a shortage of platelets as well as white and red blood cells, which results in a weakening of the immune system and, for example, a significantly higher susceptibility to infection.

    CLL is the most common form of leukemia in adults. The disease can, initially, be treated relatively well with a new class of drugs called Btk inhibitors. However, for those patients who do not respond or no longer respond to this treatment, there are usually no other effective treatment options. The result is a sharp drop in life expectancy. Since the B cells, that become tumorous, originally form an integral part of the lymphatic system, CLL is considered a type of lymphoma.

    MorphoSys’s antibody MOR208 is currently in clinical development in this indication.

  6. Multiple myeloma (MM) results from the malignant proliferation of plasma cells in the bone marrow. Healthy plasma cells contribute to immune defense by producing immunoglobulins – proteins in the human immune system that fight viruses, bacteria and other infectious agents. The disease suppresses normal hematopoiesis and weakens the body’s defenses. As the cancer primarily affects the bone marrow, bone damage is a typical sign of multiple myeloma in contrast to other blood cancers.

    Multiple myeloma is the most prevalent form of bone and bone marrow cancer in Western countries and typically occurs in the elderly. Multiple myeloma represents 10 % of all blood cancers and 1 % of all cancers worldwide. Because the infected plasma cells are part of the lymphatic system, the disease is attributed to the group of lymphomas, although lymph node involvement is rarely observed.

    MorphoSys’s antibody MOR202 is currently in clinical development in this indication.

What effect can antibodies have on blood cancer?

The main principle of antibody therapy in blood cancer is based on the specific recognition and destruction of cancer cells by making the cancer cells more visible to the immune system. Monoclonal antibodies are used for targeted therapy. These special proteins recognize so-called antigens which are exposed on the surface of certain tumor cells and "dock" specifically to these antigens. By the antibody's docking to the cancer cell, the body’s own defense system is activated to kill the cancer cell. This is known as ADCCADCC: Antibody-dependent cell-mediated cytotoxicity; a mechanism of cell-mediated immunity whereby an effector cell of the ­immune system actively destroys a target cell that has been bound by specific antibodies (antibody-dependent cell-mediated cytotoxicity). Figuratively speaking, monoclonal antibodies act on cancer cells the way a key fits into a lock, the result of which is the targeted killing of the cancer cell.

MorphoSys uses antibodies, that are made to avoid rejection by the human immune system. MorphoSys’s compounds are derived from its proprietary HuCALHuCAL: Human Combinatorial Antibody ­Library; proprietary antibody ­library enabling rapid generation of ­specific human antibodies for all ­applications and YlanthiaYlanthia: The novel next-generation antibody platform of MorphoSys antibody libraries. These are the most extensive antibody libraries in the biotechnology industry today. More than 100 therapeutic antibodies based on MorphoSys's technology are currently in development, either by MorphoSys alone and/or together with partners; 25 of these compounds are currently being studied in patients in 60 active clinical trials.

  1. Patient numbers DLBCL
  2. Patient numbers CLL
  3. Patient numbers MM
  1. Diffuse large B cell lymphoma (DLBCL) is the most common type of non-Hodgkin’s lymphoma in adults and represents about 30 % of all cases of this group of diseases.
  2. Chronic lymphocytic leukemia (CLL) is the most common type of blood cell cancer in adults in the Western world. The incidence of new cases is about four per 100,000 men and about two per 100,000 women.
  3. Multiple myeloma (MM) is the most prevalent form of bone and bone marrow cancer in Western countries, accounting for approximately 10 % of all blood cancers and 1 % of all cancers.

What role do antibodies play in combination therapies?

Combination therapy refers to the treatment of a disease with two or more drugs.

In aggressive forms of cancer, it is important to attack the tumor cells from multiple sides to kill them directly or inhibit their further growth or metastasis. Antibodies are often used in combination with other compounds, particularly in the treatment of cancer. Their very specific mode of action and their good general tolerability make them an ideal partner for a variety of therapeutics, and they can be used in various combinations over long periods of treatment.

In combination treatments, multiple mechanisms are used to tackle the tumors. This is regarded as particularly promising because not only do tumor cells often use a number of different biological mechanisms to grow and spread, but they also have the ability to develop defense mechanisms against individual therapies. The simultaneous administration of multiple therapies is intended to treat the tumor more effectively.

In addition, research has shown that certain compounds can act synergistically – where one compound increases the other’s effectiveness. This is how for instance immunomodulators, such as lenalidomide or pomalidomide, can increase the activity of natural killer cells (NK cells). Antibodies that bind to cancer cells attract these NK cells and ensure the efficient and specific killing of tumor cells.

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