4SC's Vidofludimus Meets Primary Endpoint with Excellent Response Rate in IBD Trial

Vidofludimus generates a response rate of 88.5% for the treatment of patients with Crohn's disease and ulcerative colitis

(PresseBox) (Planegg-Martinsried, Germany, ) 4SC AG (Frankfurt, Prime Standard: VSC), a drug discovery and development company focused on autoimmune and cancer indications, today announced positive preliminary results of a Phase IIa study in inflammatory bowel disease (IBD) with its lead autoimmune compound vidofludimus, an oral inhibitor of interleukin-17 (IL-17) release. The exploratory, open-label, single-arm Phase IIa ENTRANCE study met its primary endpoint of significantly increasing the response rate in corticosteroid-dependent IBD patients to 88.5% versus an average placebo response across published benchmark clinical trials of approximately 20%.

Following completion of a twelve week treatment phase with vidofludimus, disease remission was maintained in 14 out of 26 patients (53.9%) without intake of any corticosteroids (complete responders). A further 9 out of 26 patients (34.6%) remained in remission at the end of the study treatment period at a corticosteroid dose equal to or below the patients' individual threshold doses (partial responders) at which they experienced a documented disease relapse prior to entry into the study. Overall, vidofludimus significantly increased the number of patients with response (complete and partial responders = 88.5%) compared to the pre-defined placebo rate criterion of 20%. Vidofludimus was well tolerated with no critical safety issues observed. These are preliminary results prior to database lock and, therefore, subject to final review.

About the ENTRANCE Study Design

The ENTRANCE study evaluates if disease control in proven corticosteroid-dependent patients could be transferred from corticosteroids to vidofludimus as remission maintenance therapy in IBD patients. The study was conducted at 13 study centres in Germany, Bulgaria and Romania with about half of the patients being recruited in Germany. Corticosteroid-dependent male and female patients with a confirmed diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) were included into the trial. Vidofludimus was applied once daily at a 35mg oral dose over a treatment period of twelve weeks. Simultaneously, corticosteroids were attempted to be tapered down to zero during the first eight weeks of the trial period followed by a targeted corticosteroid-free treatment period of up to four weeks. Out of 34 enrolled patients, 26 were evaluable for assessment of the primary efficacy parameter which was to determine the number of patients with therapeutic response to vidofludimus (complete/partial). Complete response was defined as corticosteroid-free clinical remission in the last week of the treatment period. Partial response was defined as being in remission at any corticosteroid dose equal to or below the threshold dose of an individual patient, i.e. the steroid dose at which a patient participating in the ENTRANCE trial already had experienced a documented disease relapse prior to entering into the study. Secondary endpoints included the analysis of CDAI/CAI scores, safety, pharmacokinetic and biomarker data.

About the ENTRANCE Study Design

The ENTRANCE study evaluates if disease control in proven corticosteroid-dependent patients could be transferred from corticosteroids to vidofludimus as remission maintenance therapy in IBD patients. The study was conducted at 13 study centres in Germany, Bulgaria and Romania with about half of the patients being recruited in Germany. Corticosteroid-dependent male and female patients with a confirmed diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) were included into the trial. Vidofludimus was applied once daily at a 35mg oral dose over a treatment period of twelve weeks. Simultaneously, corticosteroids were attempted to be tapered down to zero during the first eight weeks of the trial period followed by a targeted corticosteroid-free treatment period of up to four weeks. Out of 34 enrolled patients, 26 were evaluable for assessment of the primary efficacy parameter which was to determine the number of patients with therapeutic response to vidofludimus (complete/partial). Complete response was defined as corticosteroid-free clinical remission in the last week of the treatment period. Partial response was defined as being in remission at any corticosteroid dose equal to or below the threshold dose of an individual patient, i.e. the steroid dose at which a patient participating in the ENTRANCE trial already had experienced a documented disease relapse prior to entering into the study. Secondary endpoints included the analysis of CDAI/CAI scores, safety, pharmacokinetic and biomarker data.

4SC will present these preliminary data at the BioEurope conference in Munich, Germany, on Tuesday, November 16, 2010 (10.15am CET, Room 11, Level 1), while the full data package is intended to be presented at an upcoming international IBD conference.

"We are very excited about the ENTRANCE trial results which confirmed previous activity data of vidofludimus in pre-clinical IBD models", commented Dr Ulrich Dauer, Chief Executive Officer of 4SC AG. "With a total response rate of 88.5%, vidofludimus provided substantial evidence of clinical efficacy in patients with both Crohn's disease and ulcerative colitis as a novel remission maintenance therapy."

"These study results provide a well defined basis for the positioning and development of vidofludimus as a new oral treatment option in IBD. We believe these data will also enhance the package we have already compiled for potential licensees in the pharmaceutical industry," added Dr Bernd Hentsch, Chief Development Officer of 4SC AG.

The lead investigator of the ENTRANCE trial, PD Dr Klaus Herrlinger, Department of Gastroenterology and Endocrinology at the Robert-Bosch-Hospital in Stuttgart, Germany, added: "There is a high medical need for novel IBD therapies, especially in remission maintenance therapy, since many of the drugs used today have limited efficacy or significant side effects. The results from the ENTRANCE trial are very promising. Vidofludimus could represent a viable alternative treatment option for IBD patients in the future."

For more information about the ENTRANCE trial, please visit www.clinicaltrials.gov (identifier NCT00820365).

Vidofludimus is also currently being evaluated in the randomised, double-blind, placebo-controlled Phase IIb COMPONENT study in patients with rheumatoid arthritis in combination with methotrexate. Preliminary results are expected to be reported in the first half of 2011.

Conference Call and Webcast
The senior management team of 4SC will host a conference call at 4pm CET (10am EST) today to inform about the preliminary results of the study.

Access to the presentation slides can be obtained at:
http://4sc041110-live.cyber-presentation.de

Dial-in numbers:
0800 10 12 072 (Germany)
0800 358 0886 (UK)
+1 877 941 6013 (USA)
+49 (0) 6103 485 3001 (other countries)

Conference ID: 4377221

Approximately two hours after the live presentation, an audio replay of the conference will be available on the “investors” section of www.4sc.com.

About Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the gastrointestinal tract. The main forms of IBD are Crohn's disease (CD) and ulcerative colitis (UC), which are chronic diseases constituted by acute-disease flare ups and symptom-free phases. IBD patients suffer from abdominal pain, rectal bleeding, diarrhea, weight loss, fatigue and other extra-intestinal symptoms. Although the causes of IBD are not completely understood, it is assumed that a deregulated immune response results in inflammatory mediators that attack the patient’s intestinal mucosa and trigger the symptoms.
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 therapy 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.

For both, CD and UC, the pro-inflammatory cytokine interleukin-17 (IL-17) has been demonstrated to play a crucial role in pathogenesis.

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-17), 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. Vidofludimus is currently in a Phase IIb study in rheumatoid arthritis and a Phase IIa study in inflammatory bowel disease.

4SC AG

4SC AG (ISIN DE0005753818) is a drug discovery and development company focused on autoimmune and cancer indications. Vidofludimus (4SC-101), a small molecule, is currently in a Phase IIb study in rheumatoid arthritis and a Phase IIa exploratory study in inflammatory bowel disease. The company’s lead oncology compound, resminostat (4SC-201), a pan histone deacetylase (HDAC) inhibitor, is in Phase II trials in hepatocellular carcinoma and Hodgkin’s lymphoma. Two further oncology compounds, 4SC-203 and 4SC-205, are in Phase I studies. 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.

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