4SC AG (Frankfurt, Prime Standard: VSC), a discovery and
development company of targeted small molecule drugs for autoimmune
and cancer diseases, will present pre-clinical data on vidofludimus
- its lead small-molecule drug candidate against autoimmune
diseases - in systemic lupus erythematosus (SLE) at EULAR 2011,
Europe's largest scientific conference on rheumatic diseases, in
London, UK, from May 25-28, 2011.
Vidofludimus is a novel oral inhibitor of dihydroorotate
dehydrogenase (DHODH) and of pro-inflammatory cytokine release
including interleukin-17 (IL-17A and IL-17F) as well as
interferon-gamma which is in Phase IIb development for rheumatoid
arthritis and has completed a positive Phase IIa study in
inflammatory bowel disease. Additionally, the drug candidate has
been demonstrated to be highly active in pre-clinical models of
further autoimmune diseases such as multiple sclerosis, psoriasis,
and transplant rejection. In collaboration with Prof. Dr.
Hans-Joachim Anders, Medizinische Poliklinik Innenstadt, University
Munich, Germany, the anti-inflammatory and immunosuppressive
activity of vidofludimus was directly compared to cyclophosphamide
(CYC) and mycophenolate mofetil (MMF) in an experimental animal
model of SLE (MRLlpr/lpr).
Vidofludimus was as effective as CYC and MMF in inhibiting
progression parameters of renal disease. Furthermore, vidofludimus
improved activity and chronicity indices, markers of renal
inflammation. In contrast, CYC and MMF had no significant effect on
these activity indices. Treatment with vidofludimus also
significantly reduced peribronchiolar inflammation, while CYC and
MMF failed to achieve any protection of the lung. Vidofludimus
reduced lympho-proliferation and was equipotent to CYC and superior
compared to MMF. Vidofludimus also was more effective than CYC and
MMF in reducing circulating plasma IL12p40 and tissue
auto-antibodies (IgG). In contrast to CYC and MMF, vidofludimus
showed no bone marrow toxicity effects as measured by monocyte and
neutrophil counts.
These data provide evidence that delayed onset of therapy with
vidofludimus is effective in suppressing immunopathology and
autoimmune tissue injury of MRLlpr/lpr mice. This efficacy was
comparable to CYC with respect to suppression of experimental SLE.
However, vidofludimus did not cause myelosuppression like the
unselective cell proliferation inhibitor CYC which may relate to
the more specific mode of action of vidofludimus. Vidofludimus had
a superior activity profile than MMF in this mouse model of SLE.
Thus, vidofludimus may represent a novel drug that could control
active SLE like CYC but avoid CYC toxicity and could, therefore, be
considered for induction and maintenance therapy of SLE.
Dr Bernd Hentsch, Chief Development Officer of 4SC, commented:
'In addition to vidofludimus' primary target indications rheumatoid
arthritis and inflammatory bowel disease, vidofludimus demonstrated
the potential to effectively control active SLE in an experimental
preclinical model without the type of side effects often seen with
standard therapies. Therefore, vidofludimus could be considered to
be positioned as a novel induction and maintenance therapy for
lupus, an autoimmune disease with significant unmet need and poor
therapeutic options available.'
Details of the presentation:
SAT0477: 'Vidofludimus shows a superior profile compared to
cyclophosphamide and MMF in an experimental systemic lupus
erythematosus model'Date and time: 28 May 2011 from 9:00 to 12:00
a.m.Topic: SLE, Sj�gren's and APS - etiology, pathogenesis and
animal modelsSession type: Poster SessionPresenter: Onkar
Kulkarni1, Hans-Joachim Anders1, Robert Doblhofer2, Bernd Hentsch2,
and Aldo Ammendola2
1Medizinische Poliklinik Innenstadt, University Munich, Germany;
24SC AG, Planegg-Martinsried, Germany
A copy of the poster presentation is available on the 4SC
website under:
http://www.4sc.de/product-pipeline/publications-posters.
Notes to Editor:
About Vidofludimus
Vidofludimus is a novel, orally administered small molecule for
the treatment of autoimmune disorders such as rheumatoid arthritis
and inflammatory bowel disease. The therapeutic efficacy of
vidofludimus is based on a dual principle. Vidofludimus inhibits
the expression of selected pro-inflammatory cytokines, including
interleukin-17 (IL-17A and IL-17F) and interferon-gamma, that have
crucial pathogenic roles in a variety of autoimmune diseases.
Vidofludimus also inhibits dihydroorotate dehydrogenase (DHODH), a
key enzyme of the pyrimidine biosynthesis, thereby halting the
proliferation of activated T and B cells which are involved in the
pathology of autoimmune disorders. The combination of two
mechanisms of action provides an innovative therapeutic approach
with broad clinical potential in various autoimmune diseases.
Vidofludimus is currently in clinical development for rheumatoid
arthritis and inflammatory bowel disease.
About Systemic Lupus Erythematosus
Systemic lupus erythematosus, SLE, is a systemic autoimmune
disease that can affect any part of the body. As occurs in other
autoimmune diseases, the immune system attacks the body's cells and
tissue, resulting in inflammation and tissue damage. It is a Type
III hypersensitivity reaction caused by antibody-immune complex
formation. SLE most often harms the heart, joints, skin, lungs,
blood vessels, liver, kidneys, and nervous system. The course of
the disease is unpredictable, with periods of illness (flares)
alternating with remissions. The disease occurs nine times more
often in women than in men, especially in women of child-bearing
potential, i.e. between 15 to 35 years of age, and is also more
common in those of non-European descent. Although SLE is treatable
through addressing its symptoms mainly with cyclophosphamide,
corticosteroids and immunosuppressants, there is currently no cure.
SLE can be fatal, although with recent medical advances, fatalities
are becoming increasingly rare. Survival for people with SLE in the
United States, Canada, and Europe is approximately 95% at five
years, 90% at 10 years, and 78% at 20 years. With belimumab
(benlysta), an i.v. antibody, the first novel therapy after about
50 years has been recently approved.
About 4SC
4SC (ISIN DE0005753818) discovers and develops targeted,
small-molecule drugs for the treatment of diseases with a high
unmet medical need in various autoimmune and cancer indications.
These drugs are intended to provide patients with innovative
treatment options that are more tolerable and efficacious than
existing therapies, and provide a better quality of life. The
company's balanced pipeline comprises promising products that are
in various stages of clinical development. 4SC's aim is to generate
future growth and enhance its enterprise value by entering into
partnerships with leading pharmaceutical companies.
Founded in 1997, 4SC currently has 94 employees and has been
listed on the Prime Standard of the Frankfurt Stock Exchange since
December 2005.
For further information, please visit www.4sc.com.
Legal Note
This document may contain projections or estimates relating to
plans and objectives relating to our future operations, products,
or services; future financial results; or assumptions underlying or
relating to any such statements; each of which constitutes a
forward-looking statement subject to risks and uncertainties, many
of which are beyond our control. Actual results could differ
materially, depending on a number of factors.
Language: English Company: 4SC AG Am Klopferspitz 19a 82152
Martinsried Deutschland Phone: +49 (0)89 7007 63-0 Fax: +49 (0)89
7007 63-29 E-mail:
public@4sc.com
Internet:
www.4sc.de
ISIN: DE0005753818 WKN: 575381 Listed: Regulierter Markt in
Frankfurt (Prime Standard); Freiverkehr in Berlin, Düsseldorf,
München, Stuttgart
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