4SC AG

Legal Proceedings Report • Sep 23, 2014

News Details

Corporate | 23 September 2014 07:30

Press Release: 4SC’s partner Yakult Honsha completes Phase I part of clinical study with resminostat in Asian HCC patients and starts randomised Phase II part

4SC AG / Key word(s): Miscellaneous

23.09.2014 / 07:30

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Press Release

4SC’s partner Yakult Honsha completes Phase I part of clinical study with resminostat in Asian HCC patients and starts randomised Phase II part

– Phase I confirms safety and tolerability of resminostat/sorafenib combination in the planned dose regimen in Asian HCC patients

– Phase II to compare efficacy of resminostat/sorafenib combination with current HCC standard of care (sorafenib monotherapy) in up to 140 Asian 1 st line HCC patients

Planegg-Martinsried, Germany, 23 September 2014 – 4SC AG (Frankfurt, Prime Standard: VSC), a discovery and development company of targeted small molecule drugs for cancer and autoimmune diseases, today announced that its Japanese partner Yakult Honsha Co., Ltd. has successfully completed the Phase I part and initiated the randomised Phase II part of a clinical Phase I/II study which evaluates 4SC’s epigenetic cancer compound resminostat in combination with the cancer drug sorafenib as a potential novel first-line therapy of advanced Asian HCC patients.

In the dose escalation Phase I part in 9 Asian patients with advanced HCC, the resminostat/sorafenib combination proved to be safe and well tolerated. Based on the result of the Phase I part, the multi-centre randomised Phase II part of the trial has been started. It will compare the efficacy of the resminostat/sorafenib combination with the current HCC standard therapy of sorafenib as a first-line treatment in up to 140 patients with advanced HCC. The primary endpoint will be time-to-progression (TTP). Secondary endpoints are, inter alia , overall survival (OS), progression-free survival (PFS) and safety. The study will also evaluate the ZFP64 biomarker. All patients enrolled have to be previously untreated with systemic chemotherapy.

The development of resminostat in the Japanese market is of high strategic importance to 4SC. In April 2011, 4SC has granted an exclusive license to Yakult Honsha, the Japanese market leader in gastro-intestinal cancer therapeutics, for the development and commercialisation of resminostat in Japan. After successfully completing a Phase I safety study with resminostat in Japanese patients with advanced solid tumours in May 2014, Yakult is currently investigating resminostat in two Phase I/II studies in Asia, in liver cancer (hepatocellular carcinoma, HCC) and non-small-cell lung cancer (NSCLC). HCC, a cancer with a high medical need and very limited therapeutic options, has a particularly high incidence in Japan. HCC is also the key indication of 4SC’s planned clinical development programme for resminostat in the Western world.

Enno Spillner, Chief Executive Officer of 4SC, said: “We are very pleased that our partner Yakult Honsha has completed the Phase I part of study confirming the clean safety profile of the resminostat/sorafenib combination for the first time also in Asian HCC patients. We are delighted about the great enthusiasm and energy of our Japanese partner in the development of resminostat and we look forward to the Phase II part of the study which will compare under randomised conditions the resminostat/sorafenib combination to sorafenib alone, the current standard of care for first-line treatment of HCC. In parallel, we will continue to drive forward the preparation of our own clinical development plans with resminostat in first-line HCC in the Western world.”

Ends

About Resminostat

Resminostat (4SC-201), 4SC’s lead oncology compound, is an oral histone-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, 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. Resminostat is therefore 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.

4SC is currently in preparation of the next step to develop resminostat towards market approval in first-line HCC, a randomised-controlled, double-blind Phase II study evaluating the resminostat sorafenib combination compared to the current treatment standard sorafenib, as a first line treatment of advanced HCC.

About the Resminostat Partnering Deal with Yakult Honsha for Japan

4SC granted an exclusive license to Yakult Honsha for the development and commercialization of resminostat in Japan in April 2011. 4SC has received an upfront payment from Yakult Honsha of EUR6 million and is eligible for up to EUR127 million payable upon achieving specified milestones including clinical and regulatory events in Japan. In addition to milestone payments, Yakult will pay 4SC double-digit royalties linked to product sales of resminostat. Yakult Honsha will be responsible for all clinical requirements for resminostat development in Japan in oncology indications. 4SC is aiming to partner this compound in other territories, including Europe, the USA and Asia.

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 65 employees (55 FTEs) at 30 June 2014. 4SC AG has been listed on the Prime Standard of the Frankfurt Stock Exchange since December 2005.

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, Michelle Kremer

katja.arnold(at)mc-services.eu, Tel.: +49-89-2102-2840

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:	DE0005753818
WKN:	575381
Listed:	Regulierter Markt in Frankfurt (Prime Standard); Freiverkehr in Berlin, Düsseldorf, München, Stuttgart

End of News	DGAP News-Service

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