Corporate | 8 October 2015 07:30


Press Release 4SC AG: World-renowned experts in the field of cancer therapy development discuss ‘Epigenetic Regulation of Immunogenicity’ at 10th 4SC Scientific Symposium


DGAP-News: 4SC AG / Key word(s): Conference/Miscellaneous

2015-10-08 / 07:30


Press Release

World-renowned experts in the field of cancer therapy development discuss “Epigenetic Regulation of Immunogenicity” at 10th 4SC Scientific Symposium

“Epigenetic Therapy a Vital Component in the Fight against Cancer”

Planegg-Martinsried, 8 October 2015 4SC AG (Frankfurt, Prime Standard: VSC), a biotechnology company for the research and development of targeted small molecule drugs mainly focusing on cancer, hosted its 10 th Scientific Symposium on Wednesday, 30 September 2015. Joining the event were more than 50 distinguished participants from the international scientific, clinical and industry community involved in the development of novel cancer treatment modalities. The Symposium, held at 4SC’s site in Martinsried/Munich, discussed recent advances in epigenetic drug discovery and the clinical impact of epigenetic and immune therapeutic approaches on personalized medicine.

Epigenetic alterations as well as tumour immunity represent key mechanisms in the development of cancer and are therefore considered relevant therapeutic targets. The challenge of treating, and ultimately curing, cancer and as well as the potential of combining immunotherapy with epigenetic approaches was highlighted by Prof. Andreas Mackensen, Director at the Department of Haematology & Internal Oncology at the Erlangen University Hospital, who chaired the conference and paved the way for three scientific talks around epigenetic alterations, their role in health and disease and as modulators of tumour immunity.

Prof. Thomas Jenuwein, keynote lecturer from the Max Planck Institute of Immunobiology & Epigenetics in Freiburg and the first scientist to identify a histone methylating enzyme, opened the event by highlighting that epigenetic malfunction is key to the development of cancer, as it significantly influences the timing and aggressiveness of the disease. For example, an aberrant chromatin marking of a tumour suppressor gene, which is then silenced, leads to uncontrolled proliferation of the cancer cell. This is where epigenetic therapy comes into play: inhibitors for chromatin-changing enzymes, one prominent example being histone deacetylase, short HDAC inhibitors, possess the ability to reprogram aberrant transcription, i.e. turn on tumour suppression. Epigenetic regulators can also help break the tumour’s tolerance towards the immune system, for example by triggering “anti-tumour” immune responses via the presentation of neo-antigens or maintenance of T-lymphocyte activation.

Furthermore, Prof. Jenuwein presented an Agouti mouse model demonstrating the importance of epigenetic mechanisms for the prevention of cancer. In this Agouti mouse a change in the mother’s diet had a significant corresponding influence on the offspring, indicating that epigenetic changes can also propagate to the next generations. The underlying mechanisms are not yet fully understood but most likely involve non-coding RNAs that bind their respective (complimentary) DNA sequence in order to transport epigenetic signals.

Prof. Angela Risch, Head of the Cancer Genetics/Epigenetics Division at the University of Salzburg, showcased how epigenetic characterization of cancer is already used in the clinic. For instance, epigenetic profiles (e.g. DNA methylation) can be used to predict a patient’s therapeutic outcome, which in certain tumours already outperforms standard histopathological classification. She also expanded on the clinical potential for epigenetic profiling to identify risk groups, epigenetic biomarkers for early detection or response to treatment and the inhibition of key epigenetic regulators.

Interestingly, 4SC has been able to detect a new biomarker in the blood of patients, called ZFP64, during their clinical studies with its epigenetic agent resminostat in advanced liver cancer and Hodgkin’s lymphoma. The biomarker’s expression prior to resminostat treatment has been shown to correlate with patients’ overall survival in both indications. The predictive value of the ZFP64 biomarker, however, needs to be further validated. It is currently under evaluation in ongoing clinical studies.

Translating research findings into the clinic remains a challenge. As Prof. em. Roland Mertelsmann, University Medical Center, Albert Ludwigs University Freiburg, pointed out: epigenetic regulation produces a highly variable cancer phenotype that can rapidly adapt to a changing environment and also to treatment. Cancer can only be cured if you kill the last tumour cell. In order to succeed in the fight against cancer, a patient’s own defense system must be activated; the inhibition of so-called immune checkpoints (molecules that can turn immunological signals on or off) is thought to be one way to liberate the endogenous immune system (so called “releasing the break”).

“Two hands will better grab a target than one finger”, Prof. Jenuwein noted. In fact, all three speakers agreed that the most powerful approach would certainly be a combination of checkpoint inhibition and the expression of neo-antigens on cancer cells via epigenetic therapies. In other words, strengthen the immune system and weaken the tumour, thereby rendering it more vulnerable to immune system attack.

Things had come full circle when Dr. Daniel Vitt and Dr. Susanne Danhauser-Riedl; Chief Scientic Officer and Chief Medical Officer, respectively, of 4SC elaborated on the epigenetic drug candidates in 4SC’s pipeline and how these drugs address cancer therapies. The company identified multiple features of their two clinical stage cancer drugs, i.e. resminostat and 4SC-202, which would prime cancer cells for subsequent immunotherapy. As an example and as shown in preclinical tests, resminostat enhances the immunogenicity of cancer cells as it restores the expression of ligands important for lymphocyte binding (i.e. natural killer cells and cytotoxic T cells) and tumour-associated antigens, at the same time reducing unspecific immunosuppressive mechanisms.

Enno Spillner, Chief Executive Officer of 4SC AG commented: “This symposium confirmed 4SC is on a good path in the development of its epigenetic regulators, resminostat as well as 4SC-202. In the US, HDAC inhibitors have already been approved and successfully used in the clinic. 4SC and its partners have been and/or are currently developing resminostat in a number of indications including liver, lung, pancreatic and biliary tract cancer and soon in cutaneous T-cell lymphoma (CTCL). We welcome the participation of so many international experts as well as our Asian development partners for resminostat from Yakult Honsha and Menarini AP in our Symposium.”

Summing up 4SC’s work in the field, Prof. Jenuwein concluded: “I am very happy to see the development of smart epigenetic inhibitors has been brought to such a high quality by 4SC. This biotech company is at the forefront in Germany for the successful translation of epigenetic therapy to the clinic and for the patient.”

Combination approaches provide ways toward improving existing therapies and developing new ones with the aim to provide survival benefit for larger numbers of patients. To further investigate the properties of resminostat and 4SC-202 as immunomodulators and their potential combination with immunotherapy agents, such as checkpoint inhibitors, 4SC has recently been awarded a grant from the German Federal Ministry of Education and Research of up to EUR 450,000 as part of the European Eurostars programme.

End of press release

Epigenetics
Epigenetics is currently one of the most promising approaches in the fight against cancer. Epigenetics is a term used to describe functionally relevant changes to the genome caused by external or environmental factors, which, unlike mutations, do not involve a change in the nucleotide sequence. Examples of epigenetic mechanisms include DNA methylation or histone modification, each of which alters how genes are expressed and consequently being either activated or silenced without altering the underlying DNA sequence. Alongside genetic mutations, epigenetic ‘programming errors’ are very often the reason why previously healthy cells subsequently turn cancerous. The idea is for epigenetic compounds to correct these mistakes in genetic regulation and thus interrupt or combat the mechanism that is responsible for the onset of cancer.

Epigenetics is considered by market intelligence experts as a future growth market within the pharmaceutical industry, in particular in the field of oncology. This is reflected in a report published in 2014 by the business information publisher Visiongain which forecasts that the worldwide epigenetics market will achieve revenues of some $4.3 billion in 2018, after estimated revenue of $2.5 billion generated in this segment in 2014.

About 4SC
4SC is a biotechnology company dedicated to the research and development of small-molecule drugs for treating diseases with high unmet medical needs focusing on cancer. 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 pharmaceutical and biotech companies. Founded in 1997, 4SC had a headcount of 68 employees (60 FTEs) at 30 June 2015. 4SC AG has been listed on the Prime Standard of the Frankfurt Stock Exchange (ISIN DE000A14KL72) since December 2005.

Resminostat and 4SC-202
Resminostat, 4SC’s epigenetic lead compound, is an oral histone deacetylase (HDAC) inhibitor that has already been examined in preclinical and clinical trials in indications such as liver cancer, lung cancer, Hodgkin’s lymphoma, colorectal cancer, pancreatic cancer and biliary tract cancer, and has shown promising activity as an immune modulator in initial preclinical models. 4SC is currently preparing a clinical Phase II trial with resminostat in the indication of cutaneous T-cell lymphoma (CTCL). Based on data from this study, 4SC will ideally be able to submit a filing for conditional approval for resminostat in the indication of CTCL in Europe. 4SC’s second epigenetic compound 4SC-202, a selective inhibitor of lysine specific demethylase (LSD1) and HDAC isoforms 1,2 and 3, has already undergone successful testing in a clinical Phase I trial in patients with advanced haematological tumours. 4SC-202 possesses a unique mechanism of action, namely a combination of the epigenetic regulation of gene expression and the targeted combating of cancer stem cells.

Cautionary statement regarding forward-looking statements
This press release contains certain forward-looking statements. Any forward-looking statement applies only on the date of this press release. By their nature, forward-looking statements are subject to a number of known and unknown risks and uncertainties that may or may not occur in the future and as a result of which the actual results and performance may differ substantially from the expected future results or performance expressed or implied in the forward looking statements. No warranties or representations are made as to the accuracy, achievement or reasonableness of such statements, estimates or projections, and 4SC AG has no obligation to update any such information or to correct any inaccuracies herein or omission herefrom which may become apparent.

For more information please visit www.4sc.com or contact:

4SC AG
Jochen Orlowski, Corporate Communications & Investor Relations
jochen.orlowski(at)4sc.com, Tel.: +49-89-7007-6366

MC Services
Katja Arnold, Dr Cora Kaiser
katja.arnold(at)mc-services.eu, Tel.: +49-89-210-2280

The Trout Group
Chad Rubin
crubin(at)troutgroup.com, Tel.: +1-646-378-2947





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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: DE000A14KL72
WKN: A14KL7
Listed: Regulated Market in Frankfurt (Prime Standard); Regulated Unofficial Market in Berlin, Dusseldorf, Munich, Stuttgart, Tradegate Exchange
End of News DGAP News Service

400723  2015-10-08