MOR103/GSK3196165 is a fully human HuCAL antibody directed against GM-CSF out-licensed to GSK in clinical development for inflammatory diseases.

MOR103/GSK3196165 is a fully human HuCAL antibody directed against the granulocyte-macrophage colony-stimulating factor (GM-CSF). MorphoSys discovered and advanced MOR103/GSK3196165 into clinical development, initially in rheumatoid arthritis and multiple sclerosis, and fully out licensed it to GSK in June 2013. GSK is now developing the antibody in the area of inflammatory diseases including phase 2 clinical studies in rheumatoid arthritis (RA) and inflammatory hand osteoarthritis (OA). Due to its diverse functions in the immune system, GM-CSF can be considered a target for a broad spectrum of anti-inflammatory therapies.


Mode of Action

GM-CSF stimulates stem cells to produce granulocytes and other macrophages and subsequently activates these differentiated immune cells. GM-CSF is part of the natural immune and inflammatory cascade but has also been identified as an inflammatory mediator in autoimmune disorders like rheumatoid arthritis leading to an increased production of pro-inflammatory cytokines, chemokines and proteases and thereby ultimately to articular destruction.
GM-CSF levels are significantly elevated in several inflammatory disorders and in the joints of rheumatoid arthritis patients. By neutralizing GM-CSF, the HuCAL antibody MOR103 has demonstrated its ability to reduce GM-CSF induced proliferation and activation of inflammatory cells and to intervene in several pathophysiological pathways in pre-clinical models of RA.

The figure depicts the suggested mechanism of action of MOR103/GSK3196165

The therapeutic field

Rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic, disabling and painful inflammatory condition, which can lead to substantial loss of mobility due to pain and joint destruction. The disease affects approximately four to six million people worldwide. In patients suffering from RA, white blood cells move from the bloodstream into the synovium, where they cause inflammation.
Rheumatoid arthritis is an autoimmune disease characterized by inflammation of the joints, bone and cartilage erosion, and joint deformity. Additionally, the condition manifests itself in multiple joints in the body. Although the disease primarily affects the joints, it can also affect other organs, including the skin, eyes, lungs, heart, and blood vessels. Despite the many advances in both the understanding and the treatment of the disease, it remains largely incurable, and its causes are still unknown. The disease can lead to premature mortality, disability, and decreased quality of life.




Hand osteoarthritis

Osteoarthritis (OA) is a condition that causes damage to the surface of joints in the body leading to joint pain and stiffness. In some patients it can adversely affect work and normal daily activities.


Clinical Studies

As the compound has been fully out-licensed to GSK in 2013, GSK is responsible for the further clinical development of MOR103/GSK3196165. MOR103/GSK3196165 is currently under investigation in four phase 2 trials: GSK initiated a Phase 2 study (efficacy and safety) in Rheumatoid Arthritis in 2015 and a mechanistic Phase 2 trial in combination with Methotrexate in the same indication in 2016. In January 2017, a Phase 2 study analyzing pharmacokinetics and safety in Japanese RA patients was also led by GSK. Moreover, a Phase 2a trial with patients that have developed hand osteoarthritis has been initiated in 2016.


Licensing agreement with GSK

MorphoSys and GSK entered into a global agreement to develop and commercialize MOR103/GSK3196165 in June 2013. Under the terms of the agreement, GSK has assumed responsibility for all development and commercialization of the compound. As part of the agreement, MorphoSys received an immediate upfront payment. On achievement of certain development, regulatory, commercial and sale-based milestones, MorphoSys would be eligible to receive additional payments, in addition to tiered, double-digit royalities on net sale.