Date: 2015-04-14
Type of information: Licensing agreement
Compound: resminostat (oral pan-histone deacetylase (HDAC) inhibitor)
Company: 4SC (Germany) Menarini (Italy)
Therapeutic area: Cancer - Oncology
Type agreement: development licensing
Action mechanism: enzyme inhibitor/histone deacetylase inhibitor. Resminostat is an oral pan-histone-deacetylase (HDAC) inhibitor with an innovative, epigenetic mechanism of action that enables this compound to be deployed as a novel, targeted tumour therapy for a broad spectrum of oncological indications, particularly in combination with other anti-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. Resminostat - by 4SC and its Japanese partner Yakult - has been investigated in a broad clinical campaign comprising hepatocellular carcinoma, Hodgkin's Lymphoma, colorectal cancer, and non-small-cell lung cancer. In the Phase II SAPHIRE trial in patients with advanced Hodgkin's Lymphoma, 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 hepatocellular carcinoma 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. 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. 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 commercialization of resminostat in Japan.
Disease: hepatocellular carcinoma and all oncological indications
Details: * On April 14, 2015, 4SC AG andSingapore based Menarini Asia-Pacific Holdings (“Menarini AP”) announced that they 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 among others 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 hepatocellular carcinoma.
Financial terms: 4SC will receive upfront and milestone payments totaling approximately up to € 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.
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