MorphoSys’s most advanced internal development program is MOR 103 – a therapeutic HuCAL antibody for
the treatment of rheumatoid arthritis. Approximately four to six million people worldwide suffer from this
disease. The MorphoSys antibody MOR 103 attacks a central node in the network of disease-mediating factors
and could potentially inhibit and/or limit the destruction of joints triggered by the disease, including
hand, knee, shoulder, foot, and hip joints. In 2008, MorphoSys will begin clinical development of this antibody
with tests in healthy volunteers.
Rheumatoid arthritis (RA) is a chronic inflammatory
autoimmune disease, thought to be caused by a disorder
of the immune system. The immune system is usually
able to distinguish between the body’s own tissues and
foreign bodies such as viruses or bacteria, but occasionally
it mistakenly recognizes the body’s own healthy cells as
foreign. In RA, this process mainly occurs in a membrane
called the synovial membrane, which surrounds every
mobile joint in the human body and creates a protective,
fluid-filled sac around the joint.
In the diseased joint, disruption of the normal inflammation
process results in a significant chronic swelling and ultimately
leads to destruction of the cartilage and bone tissue
as well as progressive deformation of the joint. Damage can
also occur throughout the whole body, including the skin,
blood vessels, heart, lungs, and muscles. A wide range of
immune cells builds up in the joint, which causes further
progression of the disease by stimulating the production of
various signalling molecules. MorphoSys’s drug candidate
aims to disrupt this chain of events.
The target molecule GM -CSF, a growth factor for white
blood cells that is bound by MOR103, plays a key role in the
disease process that destroys joints. GM -CSF is part of the
natural immune and inflammatory cascade, but is also an
inflammatory mediator in autoimmune processes such as
RA. In inflamed joints where GM -CSF is found in high levels,
it also contributes strongly to the release of other signalling
molecules. GM -CSF binds to its complementary receptor
on the surface of specific immune cells in the joint, stimulating
their activation and proliferation. Two categories of
white blood cells that are activated in this process, the neutrophils
and the macrophages, act directly to increase the
production of a complex network of pro-inflammatory and
pathogenic molecules in surrounding tissues, as well as further increasing the immune reaction by activating B and
T cells. These processes create an increasing vicious circle
that ultimately leads to increased destruction of the joint.
The HuCAL-derived antibody MOR103 acts to neutralize
GM -CSF, which should reduce the unwanted dispersal and
activation of the inflammatory immune cells in the diseased
joint and in this way attempts to disrupt the inflammatory
cycle.
There is specific scientific evidence that points towards
GM -CSF playing a pivotal role in RA. Injection of GM -CSF
was found to worsen arthritic symptoms in RA patients.
On the other hand, mice unable to produce the protein
GM -CSF are resistant to the induction of autoimmune
diseases. Additionally, the number of macrophages in an
inflamed joint is directly correlated with the extent of the
joint damage in human RA patients, which further validates
this target molecule. Finally, MorphoSys’s antibody
MOR103 itself has already shown various promising results
in two animal models of RA.
C o n v i n c i n g s c i e n t i f i c r e s u lt s i n a s t r o n g
m a r k e t p o s i t i o n
The market for drugs for the treatment of rheumatoid
arthritis shows very strong growth. In 2004, worldwide
sales figures for modern biopharmaceutical drugs to
treat RA were in the region of US $ 6 billion. The market is
expected to increase further to US $ 14 billion in 2009,
and is a highly competitive sector in the pharmaceutical
industry.
There is currently no cure for RA. In recent years, drugs
developed through biotechnology – among them other
therapeutic antibodies – have greatly improved the treatment
options. Despite this recent progress, the demand
for additional improved treatment methods remains huge.
The MOR103 approach mirrors that of the most successful
class of anti-inflammatory agents known to date, namely
the group of substances that neutralize the soluble cytokine
TNF (tumor necrosis factor-alpha). In this regard, MOR103 is expected to belong to the class of immunosuppressive
agents, albeit exhibiting a distinct mechanism
of action compared to the anti-TNFs. Therapeutics with
new mechanisms of action are high on the wish list of most
practicing rheumatologists.
To further improve the competitive position of MOR103,
MorphoSys has built up a strong position in intellectual
property for its program. MorphoSys announced an agreement
with the University of Melbourne in 2007, providing
the Company with exclusive access to rights covering the
use of inhibitors of GM-CSF, under a US patent application
and its progeny. Scientists Professor John Hamilton
and Professor Gary Anderson, whose discoveries are
covered in the patent application, have been leaders for
many years in the field of basic GM-CSF biology and
understanding the role of this target molecule in the progression
of RA. Their fundamental work in this area is increasingly acknowledged as the basis for targeted anti-
GM-CSF therapy.
As per evaluation by MorphoSys AG, the license acquired
by MorphoSys can lead to exclusive marketing rights
for therapeutic antibodies targeting GM -CSF in the USA.
The USA represents the lion’s share of the market for drugs
to treat RA. In addition to the licensing of this patent,
MorphoSys has filed additional patent applications for the
HuCAL-derived antibody MOR103.
The important scientific basis, the new mode of action,
and the previously available data on the target molecule
GM -CSF combine to increase MorphoSys’s confidence
in MOR103 as an attractive candidate in its portfolio for
the treatment of RA. Above all, the strong patent position
and the low level of direct competition suggest that the
approach has significant economic potential.
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Interview with Prof. Dr. Burkhardt.
Prof. Dr. Burkhardt serves as Professor of Rheumatology
and Head of the Division of Rheumatology at the University
of Frankfurt. During his career he participated in a variety
of late-stage clinical studies of biologicals such as TNF -
blocking agents, IL-1 receptor antagonists and the therapeutic
antibody Rituximab® for the treatment of RA , and
other inflammatory indications.
There are drugs already on the market for the treatment
of RA . Do you really think that more are needed?
*Prof. Dr. Burkhardt | In my opinion there is still a substantial
unmet medical need, because fewer than 25 % of
patients achieve a sustained remission, which is the best
achievable state of an RA-patient under presently available
treatment options. A large group of patients do not benefit
at all from current treatments and there are safety concerns
associated with long-term use of existing anti-TNF therapies.
These considerations are strong incentives that drive the
search for new treatment options, particularly for drugs with
innovative modes of action such as MOR103.