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MOR103 (aka GSK3196165)

MOR103 (aka GSK3196165) is a fully human HuCAL-antibody directed against GM-CSF (granulocyte-macrophage colony-stimulating factor). As the compound has been fully out-licensed to GSK in 2013, GSK is fully responsible for the further clinical development of MOR103.

MOR103 is being developed in the area of inflammatory diseases. Due to its diverse functions in the immune system, GM-CSF can be considered a target for a broad spectrum of anti-inflammatory therapies.

MOR103 in rheumatoid arthritis

Rheumatoid arthritis (RA) is traditionally considered to be a chronic, inflammatory autoimmune disorder that causes the immune system to attack the joints and affects in particular a membrane, called synovium, which lines each movable joint. It is a 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.

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 RA leading to an increased production of pro-inflammatory cytokines, chemokines and proteases and thereby ultimately to articular destruction.

In 2015 GSK initiated a clinical phase 2 study to investigate the safety and efficacy of MOR103 (in combination with MTX) in pateints with RA, followed in 2016 by the initiation of a mechanistic study also in RA patients.

Mode of Action

By neutralizing GM-CSF, the HuCAL-based antibody MOR103 has demonstrated its ability to reduce the undesired proliferation and activation of inflammatory macrophages and neutrophils and to intervene in several pathophysiological pathways in preclinical models of RA.

MOR103 in hand osteoarthritis

Osteoarthritis 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 daly activities. In 2016 GSK initiated a clinical phase 2 study to investigate the safety and efficacy of MOR103 in patients with inflammatroy hand osteoarthritis.

 

MOR103 in multiple sclerosis

Multiple sclerosis (MS) is a chronic, inflammatory autoimmune disorder that attacks the central nervous system (CNS), affecting the brain, spinal cord and optic nerves. The body’s own defense system attacks the myelin sheath that surrounds and insulates the nerve fibers in the CNS. The nerve fibers themselves can also be damaged. The damaged myelin forms scar tissue (sclerosis), which gives the disease its name. When any part of the myelin sheath or nerve fiber is damaged or destroyed, nerve impulses traveling to and from the brain and spinal cord are distorted or interrupted, producing the variety of symptoms that can occur.

GM-CSF can act as a pro-inflammatory cytokine mainly by inducing the activation, maturation and differentiation of macrophages and dendritic cells, which are essential for the initiation and propagation of cell-mediated immune responses.

Preclinical data have shown that GM-CSF could also play a central role in multiple sclerosis. Based on a compelling scientific rationale provided by the promising preclinical data, MorphoSys evaluated the compound in MS as a second indication. MOR103 has concluded a phase 1b trial in MS and data of the study were presented at the ACTRIMS-ECTRIMS meeting in September 2014.

 

Clinical Studies

GSK is currently investigating MOR103 in two phase 2 studies in patients suffering from RA as well as in a phase 2 study in hand osteoarthritis. Here you can find further information on active clinical trials.

Background

MorphoSys and GSK entered into a global agreement to develop and commercialize MOR103 in June 2013. Under the terms of the agreement, GSK assumes responsibility for all subsequent 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 (see press release)