4SC AG
Press Release: 4SC presents new immunotherapeutic activity data of its epigenetic cancer drug resminostat at the ECCO ITOC conference 2015
4SC AG / Key word(s): Research Update Press Release 4SC presents new immunotherapeutic activity data of its epigenetic cancer drug resminostat at the ECCO ITOC conference 2015 Planegg-Martinsried, Germany, 26 March 2015 – 4SC AG (Frankfurt, Prime Standard: VSC), a discovery and development company of targeted small molecule drugs for cancer and autoimmune diseases, today presents new data on immunotherapeutic effects achieved with 4SC’s epigenetic cancer drug resminostat. The selected presentation will be held today, 26 March 2015, 11:00am CET at the ECCO ITOC conference 2015 in Munich, Germany. The presentation will cover new preclinical data demonstrating immunomodulating effects of the HDAC inhibitor resminostat, thus potentially further contributing to its anti-tumoral activity, in particular enhancing response rates. Resminostat has shown multiple positive effects both by re-programming cancer cells and by enhancing the immune system’s defence mechanism against cancer cells. The data indicate the ability of resminostat to help considerably improve the effect of checkpoint inhibitors (PD1/PDL1) and other immunotherapeutic approaches in oncology such as antibodies (e.g. rituximab) or immunostimulating agents (e.g. TLR ligands), when applied in combination therapy with these drugs in the clinic. Dr Daniel Vitt, Chief Scientific Officer and Chief Development Officer of 4SC, said: “We are highly excited about the new data demonstrating multiple immunotherapeutic effects of our lead oncology product resminostat. We believe that this data potentially opens up new avenues for safe and efficacious combination therapies with immune checkpoint inhibitors and immunotherapeutic antibodies. We are currently further evaluating the data in animal models and we are excited to be creating potential further clinical options in the future.” The scientific findings in detail Resminostat effects on mechanisms affecting anti-tumoral immune responses were analysed in hepatocellular HepG2, Huh7, and SNU475 and adenocarcinomic A549 cellular systems. It was shown that resminostat strongly reduced the expression of immunosuppression mediating enzymes, IDO1 and ARG1 thus rendering the tumor microenvironment sensitive against immune cell based anti tumor activities. In clinical treatment practice this could increase the number of patients responding to immunotherapeutic treatments, in particular check inhibitors like PD1 and CTLA4 inhibitors. Additionally, resminostat considerably enhanced the expression of several cancer antigens and MHC class I molecules, on several tumor cell lines thus making tumour cells more visible for recognition by the T cells of the immune system which in consequence leads to a more efficacious elimination of the tumour cells. Finally, upregulation of NK cell ligands and a strong boost of NK cells (natural killer cells of the immune system) by resminostat completes the new discoveries on epigenetic impact on immunotherapy. Ends Details of the Presentation: Presentation Title: Immunomodulatory characteristics of Resminostat, a novel HDAC inhibitor in phase II clinical development About resminostat Resminostat (4SC-201) is an oral protein-deacetylase (HDAC) inhibitor with an innovative epigenetic mechanism of action that potentially enables the compound to be deployed as a novel, targeted tumour therapy for a broad spectrum of oncological indications, both in monotherapy and, in particular, in combination with other cancer drugs. Like other epigenetic therapies, resminostat has been shown to modify transcription of genes in cancer cells and, thereby, to reprogram the phenotypes of such cancer cells. Additionally, resminostat has immunotherapeutic effects by activating NK cells, restoring MHCI and MHCII proteins and suppression of unspecific immunosuppression. Resminostat is assumed to be able to halt tumour progression and induce tumour regression. Furthermore, due to its epigenetic mode of action resminostat is supposed to develop additional synergetic effects when combined with classical cancer therapies and thus also fight the development of tumour cell resistance. For example, in preclinical trials, resminostat has shown that it effectively inhibits epithelial-mesenchymal transition (EMT). EMT, which may be promoted through the administration of certain conventional cancer therapies, leads to the formation of particularly aggressive tumour cells, which ultimately may result in greater proliferation of cancer cells in patients and the patients’ death. On the whole, a reinforcing positive therapeutic effect is expected to be achieved through well-tolerated parallel administration of a traditional cancer therapy and an epigenetic compound such as resminostat. Resminostat – by 4SC and its Japanese partner Yakult – has been investigated in a broad clinical campaign comprising liver cancer (hepatocellular carcinoma, HCC), Hodgkin’s Lymphoma (HL), colorectal cancer (CRC), and non-small-cell lung cancer (NSCLC). In the Phase II SAPHIRE trial in patients with advanced Hodgkin’s Lymphoma (HL), resminostat monotherapy has demonstrated anti-tumour activity, with an overall response rate of 34% and a clinical benefit in 54% of the patients in a heavily pre-treated patient population together with very good safety and tolerability. In the Phase IIa SHELTER study resminostat has been evaluated as monotherapy and in combination with sorafenib as a second-line treatment in advanced HCC after proven radiological disease progression under first-line sorafenib therapy. Patients receiving the resminostat/sorafenib combination therapy showed a median overall survival of 8.1 months. The resminostat/sorafenib combination therapy had shown a progression-free survival rate (PFSR) after 12 weeks of 70.0% and a median PFS of 5.4 months. Notably, in both tumour indications, HCC and HL, gene expression levels of the new biomarker ZFP64 measured prior to study treatment start in blood cells of patients, were identified to be potentially indicative of survival outcome upon treatment with resminostat. Hereby, the set of patients with a high level of ZFP64 gene expression at baseline showed a statistically significant increase of median overall survival compared with patients with low ZFP64 expression levels. Resminostat was further studied in a Phase I dose escalation approach in advanced colorectal cancer (CRC) patients evaluating resminostat in combination with the standard chemotherapeutic FOLFIRI regimen. Positive results for safety and tolerability as well as promising signs of clinical activity of this combination were published at the 2013 ASCO conference. Yakult Honsha is currently developing resminiostat in two randomised clinical Phase II trials in Japanese and Korean patients in the indications of HCC and NSCLC. About 4SC The Group managed by 4SC AG (ISIN DE0005753818) discovers and develops targeted, small-molecule drugs for treating diseases with high unmet medical needs in various cancer and autoimmune indications. These drugs are intended to provide innovative treatment options that are more tolerable and efficacious than existing therapies, and provide a better quality of life. The Company’s 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 and biotech companies. Founded in 1997, 4SC had a headcount of 66 employees (57 FTEs) at 31 December 2014. 4SC AG has been listed on the Prime Standard of the Frankfurt Stock Exchange since December 2005. Cautionary statement regarding forward-looking statements For more information please visit www.4sc.com or contact: 4SC AG MC Services The Trout Group 2015-03-26 Dissemination of a Corporate News, transmitted by DGAP – a service of EQS Group AG. The issuer is solely responsible for the content of this announcement. The DGAP 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 | ||
Germany | ||
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: | Regulated Market in Frankfurt (Prime Standard); Regulated Unofficial Market in Berlin, Dusseldorf, Munich, Stuttgart | |
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