4SC AG (Frankfurt, Prime Standard: VSC), a drug discovery and development company, today announced that the first patient has been dosed in the Phase I/II SHORE study with the oral pan-histone deacetylase (HDAC) inhibitor resminostat as a second-line treatment for patients with advanced and metastatic colorectal KRAS-mutant cancer.

SHORE is a randomised, open-label, multi-centre, two-arm Phase I/II study in 70 patients that will evaluate the efficacy, safety and pharmacokinetics of resminostat, in combination with FOLFIRI, a chemotherapy regimen for the treatment of colorectal cancer, versus FOLFIRI alone in the control arm. In the combination arm of the study patients will be treated with the maximum tolerated dose of resminostat in combination with FOLFIRI, which will be determined through an initial dose-escalation phase, evaluating 200mg, 400mg, 600mg and 800mg of reminostat together with FOLFIRI in approximately 20 patients. An optional extension to this dosing scheme has been included to also evaluate 300mg, 500mg and 700mg of reminostat once daily, as well as 300mg and 400mg resminostat twice daily, each dose in combination with FOLFIRI. In the combination arm resminostat will be given orally over five consecutive days (d1-5), followed by a nine day (d6-14) treatment free period resulting in treatment cycles of 14 days (5+9 scheme) each. FOLFIRI will be given on day three and four (d3 and d4) of each of these 14 day treatment cycles. In both study arms, treatment may continue until there is evidence of progressive disease or the patient leaves the trial for other reasons. The study will be performed at approximately ten centres in Germany.

The primary endpoint of the study is to determine the progression free survival (PFS). The secondary endpoints include progression free survival rate (PFSR) after eight weeks and every eight weeks thereafter, the analysis of time-to-progression (TTP), overall survival (OS), analysis of drug safety, tolerability, pharmacokinetics and the investigation of biomarkers.

In recent years it has been discovered that colorectal cancer patients with KRAS mutant tumours do not respond to treatment with EGFR inhibitors. This has changed treatment practices, resulting in treatment with EGFR inhibitors targeting only patients with KRAS wild type tumours. As a result, a new treatment need has arisen for patients that carry mutated KRAS genes, which account for approximately 40% of metastatic colorectal cancer patients.

HDAC enzymes have emerged as promising targets in colorectal cancer over the last decade, since they have proven to be important for colon cancer cell survival. Based on both in vitro and in vivo testing it has been shown that especially the frequently observed high expression of HDAC-2 in colon cancer cells is associated with their enhanced survival capability. Resminostat, as a pan-HDAC inhibitor, reduces the activity of a variety of HDAC enzymes, including HDAC-2. Consequently, resminostat yielded promising results in preclinical models of colorectal cancer, as it also sensitized colorectal cancer cells to standard chemotherapeutics.

'By evaluating the efficacy of resminostat in patients carrying KRAS-mutant tumours, we hope to open a second-line treatment option for this colorectal cancer patient population where there is an increased unmet medical need since they cannot be treated with current EGFR targeting agents,' stated Bernd Hentsch, Chief Development Officer. 'With the commencement of the SHORE study we have delivered on our clinical development strategy for resminostat, which is assessing its efficacy in mono- and combination therapy in hematological and solid tumours. We are very excited about 2011, as we expect Phase II results for both the hepatocellular cancer SHELTER study and the Hodgkin's lymphoma SAPHIRE study.'

More information about this trial can be found on www.clinicaltrials.gov.

About Resminostat (4SC-201)

Resminostat (4SC-201) is an oral pan-histone-deacetylase (HDAC) inhibitor. HDAC inhibitors modify the DNA structure of tumour cells to cause their differentiation and programmed cell death (apoptosis) and are therefore considered to offer a mechanism of action that has the particular potential to halt tumour progression and induce tumour regression. Resminostat is currently in Phase II studies as a second line treatment for advanced hepatocellular carcinoma and colorectal cancer in KRAS-mutant patients as well as a third-line treatment in Hodgkin's lymphoma. In a completed Phase I trial in patients with various different cancer types, stable disease was achieved in over 50% of the patients, whilst the treatment was well tolerated and showed a positive, differentiating pharmacological profile to other drugs in this class.

About Colorectal Cancer Colorectal cancer is the second leading cause of death from cancers in the western world. It incorporates colon cancer, which is based in the large intestine (colon), the lower part of your digestive system. It also includes rectal cancer, which affects the last inches of the colon. Colon cancer is 2.5 times more common than rectal cancer, while rectal cancers account for fewer than 4% of all lower gastrointestinal cancers.

Current treatment of advanced colorectal cancer is based on chemotherapy regimens, such as FOLFIRI and FOLFOX, in combination with targeted antibodies, frequently as a first line treatment. These antibodies inhibit various growth factors or receptors that are involved in the progress of the cancer disease. Currently these approaches focus on targeting vascular endothelial growth factor (VEGF), an angiogenic signaling protein or epidermal growth factor receptors (EGFR).

About 4SC

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 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), a pan-histone deacetylase (HDAC) inhibitor, is in Phase II trials in hepatocellular carcinoma, Hodgkin's lymphoma and KRAS-mutant colorectal cancer. 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.

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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