MorphoSys announces publication of first MOR103 data

MorphoSys AG announced today the publication of a first data package for its most advanced proprietary drug development program MOR103, a fully human HuCAL antibody directed against GM-CSF, in the journal "Molecular Immunology".

The data presented show that MOR103 is able to block disease-relevant processes such as GM-CSF dependent proliferation and signal transduction in vitro. Additionally, the publication describes that MorphoSys was able to achieve a 5,000-fold increase in affinity and a 2,000-fold increase in potency compared to the parental antibody using its established optimization technology. With a resulting affinity - or binding strength - of 400 femtomolar, MOR103 represents the first known anti-GM-CSF agent with a subpicomolar affinity for its target. Targeting of antigens, which are present only at low concentrations in patients such as GM-CSF, will require antibodies with low picomolar to subpicomolar affinities in order to reach efficacy in vivo at low dose levels. The high affinity is also expected to lead to a beneficial dosing regimen and cost of goods advantage.

MOR103 is currently tested in a Phase 1 clinical trial to assess safety, tolerability and the pharmacokinetics of this fully human high affinity anti-GM-CSF HuCAL antibody. MorphoSys intends to present pre-clinical data for MOR103 at the HAH - Human Antibodies and Hybridomas Conference on November 12, 2008 in New York, USA, as well as at the IBC's 19th Annual International Antibody Engineering Conference on December 9, 2008 in San Diego, USA.

"We are very pleased with the results we have seen so far with MOR103 and the generation process stands out as a showcase for MorphoSys's antibody generation capabilities using our HuCAL technology," commented Dr. Marlies Sproll, Chief Scientific Officer of MorphoSys. "While the antibody's affinity is merely one feature which influences its capability as a drug we believe based on the overall data we have generated so far that MOR103 represents a very promising therapeutic candidate in our pipeline."

Rheumatoid arthritis (RA) is traditionally considered 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. As a systemic disease, RA often affects extra-articular tissues throughout the body including the skin, blood vessels, heart, lungs, and muscles. The disease affects approximately 4-6 million people worldwide. In patients suffering from RA, white blood cells move from the bloodstream into the synovium. Here, these blood cells appear to play an important role in causing the synovial membrane to become inflamed. The HuCAL-based antibody MOR103 targets GM-CSF as a means to treat inflammatory diseases such as psoriasis, multiple sclerosis (MS), chronic obstructive pulmonary disease (COPD), asthma, and especially RA. The granulocyte macrophage colony-stimulating factor (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. By neutralizing GM-CSF the HuCAL-based antibody MOR103 reduces undesired proliferation and activation of inflammatory granulocytes and macrophages and intervenes in several pathophysiological pathways.