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

(PresseBox) ( Martinsried, )
- Phase I confirms safety and tolerability of resminostat/docetaxel combination in the planned dose regimen in Asian NSCLC patients
- Phase II to compare efficacy of resminostat/docetaxel combination with docetaxel monotherapy in up to 100 Asian 2nd and 3rd line NSCLC patients

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 docetaxel as a potential novel second- and/or third-line therapy of advanced Asian NSCLC patients.

In the dose escalation Phase I part in nine Asian patients with advanced, metastatic, or recurrent NSCLC who have previously received one platinum-based chemotherapy, the resminostat/docetaxel combination proved to be safe and well tolerated in all dose levels tested. This is a key prerequisite of the further clinical development of the resminostat/docetaxel combination in this patient group.

Upon the positive Phase I results, the randomised Phase II part has started. It will compare the efficacy of docetaxel alone - a standard chemotherapeutic regimen for NSCLC - with the combination therapy of resminostat and docetaxel in the enrolled NSCLC patients. The primary endpoint of the Phase II part is progression-free survival (PFS), secondary endpoints include response rate (RR), overall survival (OS), and safety.

Enno Spillner, Chief Executive Officer of 4SC, said: "We are delighted that our partner Yakult Honsha has completed the Phase I part of the NSCLC study confirming once again the clean safety profile of our epigenetic agent resminostat when administered in combination with a classical anti-cancer drug. Lung cancer is the leading cause of cancer-related mortality around the world. Following the development progress of resminostat in this indication of high medical need is exciting. We very much appreciate the great enthusiasm of our Japanese partner in the development of resminostat."

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 non-small-cell lung cancer (NSCLC)

Lung cancer is accounting for more than any other cancer deaths in men and women worldwide. NSCLC is the most common type of lung cancer, accounting for more than 85% of lung cancer cases. Despite advances in the treatment of the disease and declining death rates over the last years in lung cancer, outcomes remain poor for NSCLC patients. Most patients are treated with surgery, either alone or in combination with chemotherapy, since NSCLC is usually not very sensitive to chemotherapy and/or radiation. The most popular drugs used for the treatment of NSCLC are targeting angiogenesis or the epidermal growth factor receptor (EGFR). Patients with a more advanced disease are primarily treated with a platinum based chemotherapy.

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 EUR 6 million and is eligible for up to EUR 127 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. The development of resminostat in the Japanese market is of high strategic importance to 4SC. 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.

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
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