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EULAR 2011 - Vidofludimus Superior to Cyclophosphamide and MMF in an Experimental Systemic Lupus Erythematosus Model

Preclinical data presented at EULAR 2011

PLANEGG-MARTINSRIED, Germany--(BUSINESS WIRE)--May 27, 2011 - 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, Sjögren's and APS - etiology, pathogenesis and animal models
Session type: Poster Session
Presenter: 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:

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.

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Posted: May 2011