PLANEGG-MARTINSRIED, Germany I July 25, 2013 I 4SC AG (Frankfurt, Prime Standard: VSC), a discovery and development company of targeted small molecule drugs for cancer and autoimmune diseases, today announced that the first patient has been treated with resminostat in a Japan-based Phase I/II lung cancer (non-small-cell lung cancer, NSCLC) clinical study conducted by its exclusive Japanese partner Yakult Honsha. The multi-centre and randomised study will investigate safety and efficacy of resminostat in combination with the cancer drug docetaxel vs. docetaxel alone in up to 118 patients in total with advanced, metastatic, or recurrent NSCLC who have previously received one platinum-based chemotherapy.
The dose-escalation Phase I part of the study will assess safety, tolerability and pharmacokinetics as well as determine the maximum tolerated dose (MTD) and potential dose-limiting toxicities (DLT) of the resminostat/docetaxel combination in order to determine a recommended dose (RD) for the Phase II part.
The randomised Phase II part 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. In a 21 day cycle docetaxel (75 mg/m2 body surface area, administered intravenously on Day 1) will be given either as monotherapy in the control arm or in combination with resminostat (up to 600 mg/day, orally administered on Days 1-5) in the second study arm. Depending on the nature of potential side-effects observed, the dose of docetaxel may be reduced. The primary endpoint of the Phase II part is progression-free survival (PFS), secondary endpoints include response rate (RR), overall survival (OS), and safety.
In 2011, 4SC granted an exclusive license to Yakult Honsha, the Japanese market leader in gastro-intestinal cancer therapeutics, for the development and commercialization of resminostat in Japan. In 2012 Yakult Honsha started the clinical development of resminostat in Japan with a Phase I study in solid tumours followed in 2013 by a Phase I/II study in first-line treatment of advanced liver cancer (hepatocellular carcinoma, HCC).
Enno Spillner, Chief Executive Officer of 4SC AG, said: 'We very much appreciate that our partner Yakult Honsha has started developing resminostat in NSCLC. After HCC and CRC, this is now the third solid cancer indication in which our new epigenetic drug has been introduced into clinical evaluation. Lung cancer is the leading cause of cancer-related mortality around the world, so we are excited to follow the development of resminostat in yet another indication of both high medical need and large market potential.'
Bernd Hentsch, Chief Development Officer of 4SC AG, added: 'There is intriguing evidence in the literature that inhibition of histone deacetylases (HDACs) may be effective in the treatment of lung cancer. Although many drugs have been tested in NSCLC, the medical need in this indication is still very high due to the heterogeneity of this group of cancers and its relative insensitivity to standard chemotherapy regimens. Therefore, the combination approach applied in this study again attempts to make use of the so far observed good ability of resminostat to be combined with a variety of other standard anti-tumor agents.'
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.
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, both in monotherapy and, in particular, in combination with other cancer drugs. HDAC inhibitors have been shown to 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. Additionally, resminostat is also assumed to induce what is known as tumour cell (re-)sensitisation to other anti-cancer compounds. This process can suppress or reverse certain tolerance and resistance mechanisms, which tumour cells often develop against other cancer drugs. Supplementary treatment with resminostat can be expected to restore or significantly improve the efficacy of a previously administered cancer therapy which was no longer effective; furthermore, combining resminostat and common cancer drugs right from the very beginning can also be expected to effectively enhance the success of such a treatment.
Resminostat to date has been investigated in a broad clinical campaign comprising liver cancer (hepatocellular carcinoma, HCC), Hodgkin's Lymphoma (HL), and colorectal cancer (CRC), with non-small-cell lung cancer (NSCLC) now adding a third solid cancer indication to the programme.
In the Phase II SAPHIRE trial in patients with advanced Hodgkin's Lymphoma (HL), resminostat in monotherapy has demonstrated substantial 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 II 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, a value to the company's best knowledge not reached in any study with a comparable second-line patient population. 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. The primary study endpoint was achieved ahead of schedule in both the combination and the monotherapy group. Furthermore, in the Phase I dose escalation part of the SHORE study, which has evaluated resminostat in combination with the chemotherapeutic FOLFIRI regimen in advanced CRC patients, positive results for safety and tolerability as well as promising signs of clinical activity of this combination has been published at the 2013 ASCO conference.
4SC is currently in discussions with regulatory agencies and potential partners in order to prepare the next clinical steps to develop resminostat in combination with sorafenib in a pivotal programme in first-line HCC towards market approval.
About the resminostat partnering agreement 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.
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 83 employees at 30 June 2013. 4SC AG has been listed on the Prime Standard of the Frankfurt Stock Exchange since December 2005.
SOURCE: 4SC AG