4SC AG — Environmental & Social Information 2011

May 9, 2011

News Details

Corporate | 9 May 2011 07:30

4SC’s Vidofludimus Inhibits IL-17 Production by Interference With the JAK/STAT and NF-kB Pathways

4SC AG / Key word(s): Miscellaneous

09.05.2011 / 07:30

Planegg-Martinsried, Germany – 9 May, 2011 – 4SC AG (Frankfurt, Prime

Standard: VSC), a drug discovery and development company focused on

autoimmune and cancer indications, has presented novel data on the

mechanism of action of vidofludimus, an oral inhibitor of interleukin-17

(IL-17A and IL-17F) release and DHODH. These data show that vidofludimus

inhibits STAT3 and NF-kB signaling pathways in murine colitis models and

were presented at Digestive Disease Week, the world’s largest

gastroenterology conference, held from May 7-10, 2011 in Chicago, USA. In

addition, final results from the previously announced vidofludimus Phase

IIa study in inflammatory bowel disease (the ‘ENTRANCE’ trial) were also

presented.

The novel mechanism of action data, generated in collaboration with Prof.

Leo R. Fitzpatrick (Department of Pharmacology, Penn State College of

Medicine, Hershey, PA), demonstrated the inhibition of IL-17 release, a key

pro-inflammatory cytokine, as well as the attenuation of STAT3 and NF-kB

signaling pathways, which play a prominent role in IL-17 production and

intestinal inflammation. Vidofludimus has previously demonstrated

inhibition of colonic IL-17 expression and murine colitis (Fitzpatrick et

al, Inflammatory Bowel Diseases, 2010).

In mouse splenocytes, vidofludimus reduced the expression of

phosphoproteins (JAK2, STAT3, and AKT1) involved in STAT3 signaling as well

as the nuclear binding of STAT3. Vidofludimus did not reduce the

phosphorylation or degradation of IkB, but inhibited nuclear binding of

p65. Phospho STAT3 and p65 immunostaining was attenuated in leukocytes

within the colons of TNBS mice treated with vidofludimus. Based on this

data it is assumed that vidofludimus inhibits IL-17 production via

interference with the JAK2/STAT3 and NF-κB pathways contributing to the

demonstrated anti-colitis activity of this drug.

The Phase IIa ENTRANCE trial, which evaluated vidofludimus as a maintenance

therapy to prevent future flare ups in inflammatory bowel disease patients,

demonstrated an 88.5% total response rate versus an average placebo

response rate of approximately 20% across published benchmark clinical

trials. 53.9% (14 out of 26) of patients were complete responders, 34.6% (9

out of 26) of patients were partial responders, and 11.5% (3 out of 26) of

patients were evaluated as non-responders. No variation in response rates

across the sub-disease populations of Crohn’s disease (85.7%) and

ulcerative colitis (91.7%) was observed. Vidofludimus was safe and well

tolerated by all patients.

Dr Bernd Hentsch, Chief Development Officer of 4SC, commented:

‘Vidofludimus has produced encouraging, positive Phase IIa results in the

ENTRANCE study in patients suffering from inflammatory bowel disease.

Together with the developing scientific framework regarding vidofludimus’

mechanism of action and influence in the modulation of cytokine expression,

we believe that our novel, oral agent has the potential to become an

important small molecule therapy for inflammatory bowel disease and other

autoimmune diseases. We are currently anticipating the results for

vidofludimus from the Phase IIb COMPONENT trial in rheumatoid arthritis

which will be reported in this quarter.’

Details of the Presentations:

1021714: ‘Inhibition of IL-17 Release by the Novel Anti-Inflammatory Drug

Vidofludimus Involves Attenuation of STAT3 and NF-kappa B Signaling

Pathways in Murine Splenocytes and Hapten-Induced Colitis’

Session date and time: May 10, 2011 from 8:00 AM to 5:00 PM

Session title: IBD: Cytokines, Signaling and Receptors

Session type: Poster Session

Presenter: Leo R. Fitzpatrick1, Jeffrey S. Small1, Aldo Ammendola2

1Pharmacology, Penn State College of Medicine, Hershey, PA, USA; 24SC AG,

Planegg-Martinsried, Germany

1034088: ‘Efficacy, Safety and Tolerability of Vidofludimus in Patients

with Inflammatory Bowel Disease: the ENTRANCE Study’

Session date and time: May 9, 2011 from 8:00 AM to 5:00 PM

Session title: IBD: Uncontrolled Clinical Observations

Session type: Poster Session

Presenter: K.R. Herrlinger1, M. Diculescu2, K. Fellermann3, H. Hartmann4,

S. Howaldt5, R. Nikolov6, A. Petrov7, W. Reindl8, J.M. Otte9, S. Stoynov10,

U. Strauch11, A. Sturm12, R. Voiosu13, A. Ammendola14, B. Dietrich14, B.

Hentsch14, E.F. Stange1

1Robert-Bosch-Hospital, Department of Gastroenterology, Hepatology and

Endocrinology, Stuttgart, GERMANY; 2Elias University Emergency Hospital,

Bucharest, ROMANIA; 3University of Schleswig-Holstein, Campus Lübeck,

Lübeck, GERMANY; 4Gastroenterologische Gemeinschafts¬praxis, Herne,

GERMANY; 5Gastroenterologische Schwerpunktpraxis, Hamburg, GERMANY; 6MHAT

Sv Ivan Rilski, Sofia, BULGARIA; 7MHAT Tokuda Hospital Sofia, Sofia,

BULGARIA; 8Technical University Munich, Munich, GERMANY; 9University of

Bochum, St. Josef-Hospital, Bochum, GERMANY; 10MHAT Tsaritsa Ioanna, Sofia,

BULGARIA; 11University Hospital Regensburg, Medical Clinic I, Regensburg,

GERMANY; 12University Hospital Charité, Campus Virchow, Berlin, GERMANY;

13Colentina Clinical Hospital, Bucharest, ROMANIA; 144SC AG,

Planegg-Martinsried, GERMANY

Copies of the presentations are available on the 4SC website under:

http://www.4sc.de/product-pipeline/publications-posters.

For more information please contact:

4SC AG

Yvonne Alexander

Investor & Public Relations

Tel.: +49 (0) 89 70 07 63 66

MC Services (Europe)

Raimund Gabriel

Tel.: +49 (0) 89 21 02 28 30

The Trout Group (USA)

Chad Rubin

Tel.: +1 646 378 2947

Notes to Editor:

About Vidofludimus

Vidofludimus (4SC-101) 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

interleukin-17 (IL-17A and IL-17F), a pro-inflammatory cytokine that has a

crucial pathogenic role 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.

About Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is a group of inflammatory conditions of

the gastrointestinal tract. The main forms are Crohn’s disease (CD) and

ulcerative colitis (UC). These chronic diseases are constituted by

acute-disease flare ups which include abdominal pain, rectal bleeding,

diarrhoea, weight loss, fatigue and other extra-intestinal symptoms and

symptom-free phases. It is assumed that a deregulated immune response

results in inflammatory mediators that attack the patient’s intestinal

mucosa and trigger the symptoms. For both, CD and UC, the pro-inflammatory

cytokine IL-17 has been demonstrated to play a crucial role in

pathogenesis.

CD is characterised by an inflammatory affliction of part or the whole of

the digestive tract and is currently incurable. Approximately 0.9 million

people in the seven major industries suffer from various CD symptoms and

mostly contract the disease between the ages of 20 and 40. CD leads to a

considerable reduction in quality of life, but may also involve severe

complications requiring immediate surgery. Current therapeutic options for

patients are largely limited to the use of anti-inflammatory

corticosteroids or immunosuppressants applied either systemically or

locally for the treatment of the symptoms, as well as the application of

biological agents (e.g. TNF-alpha targeting antibodies).

UC afflicts specifically the large intestine or colon that includes

characteristic ulcers or open sores. UC occurs in approximately 1.4 million

patients in the seven major industries and is currently treated with

anti-inflammatory drugs, immunosuppressants and biological agents targeting

specific components of the immune response. Colectomy (partial or total

removal of the large bowel through surgery) is occasionally necessary and

is considered to be a cure for the disease.

About 4SC

4SC AG (ISIN DE0005753818) discovers and develops targeted small molecules

for autoimmune and cancer indications. Vidofludimus (4SC-101), an oral

IL-17 and DHODH inhibitor, is currently in Phase II development in

rheumatoid arthritis and inflammatory bowel disease (IBD), for which

positive results from a Phase IIa study were recently reported. The

company’s lead oncology compound, resminostat (4SC-201), an oral

pan-histone deacetylase (HDAC) inhibitor, is in Phase II trials in

hepatocellular carcinoma (the most common form of liver cancer), Hodgkin’s

lymphoma and KRAS-mutant colorectal cancer. 4SC has further oncology

products in Phase I development, including 4SC-202, 4SC-203 and 4SC-205.

4SC develops drug candidates until proof-of-concept in order to generate

value creating partnerships with the pharmaceutical industry in return for

advance and milestone payments as well as royalties.

Founded in 1997, 4SC 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.

End of Corporate News

———————————————————————

09.05.2011 Dissemination of a Corporate News, transmitted by DGAP – a

company of EquityStory AG.

The issuer is solely responsible for the content of this announcement.

DGAP’s Distribution Services include Regulatory Announcements,

Financial/Corporate News and Press Releases.

Media archive at www.dgap-medientreff.de and www.dgap.de

———————————————————————

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

End of News DGAP News-Service

———————————————————————

123482 09.05.2011