Germany based 4SC AG, a discovery and development company of targeted small molecule drugs for cancer and autoimmune diseases, and Singapore based Menarini Asia-Pacific Holdings Pte. Ltd. (Menarini AP) have entered into a licensing and development partnership for 4SC's cancer compound resminostat for the Asia-Pacific region excluding Japan (APAC).
Menarini AP, a member of the world's largest Italian biopharmaceutical group, the Menarini Group, will receive the exclusive licensing rights for the development and marketing of resminostat in all APAC countries, including China, South Korea, Australia, Thailand, Philippines, Indonesia, and Vietnam.
Menarini AP will be responsible for the clinical development, regulatory approval and commercialization of resminostat in China, and other territories included in the agreement, in all oncological indications, and in particular liver cancer (HCC).
4SC will receive upfront and milestone payments totaling approximately up to Euro 95 million from Menarini payable upon achieving specified development, regulatory and commercialization milestones. In addition, 4SC will be eligible to double-digit royalties linked to product sales of resminostat.
The development of resminostat in APAC, and China in particular, is of key strategic importance to 4SC. Liver cancer (hepatocellular carcinoma, HCC), a large cancer indication with limited theraputic options and one of the lead indications of resminostat's clinical development programme, has an extremely high incidence in this region.
More than 75% of all HCC cases occur in the APAC region, largely in association with chronic hepatitis B virus (HBV) infection.
Approximately 50% of HCC cases globally occur in China alone. HCC is currently the fifth most common cancer worldwide and the third most common cause of cancer-related mortality. The incidence of HCC cases globally is expected to grow significantly from about 700,000 in 2014 to over 1 million in 2030, according to Globocan.
Enno Spillner, chief executive officer of 4SC, said "We are delighted to be entering into this partnership with Menarini. This is a further step in the clinical development of our lead compound resminostat for Asia, which is an important market with significant and growing medical need - in particular in the indication of liver cancer. Menarini, a multinational pharma player of European origin, has a strong footprint in the APAC region. We are convinced that Menarini AP, with its vast commercial experience in Asia and broad capabilities in clinical development and regulatory processes, is a perfect partner for us and an ideal complement to our existing resminostat partner Yakult Honsha in Japan."
John Graham, chief executive of Menarini AP, said "Oncology represents a strategic area of focus for the Menarini Group. We are delighted to be embarking on a partnership with 4SC in Asia on resminostat that offers promise as a therapeutic option in liver cancer, among others, one of the most prevalent forms of cancer in Asia and one with the highest unmet need."
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.
Generally, 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.
Resminostat is partnered with Yakult Honsha for Japan and with Menarini in China and the Asia Pacific (APAC) region excluding Japan.
Menarini Asia-Pacific is part of the world's largest Italian biopharmaceutical company with a heritage of over 129 years and over 16,000 employees in more than 100 countries.
The Group managed by 4SC AG discovers and develops targeted, small-molecule drugs for treating diseases with high unmet medical needs in various cancer and autoimmune indications.