On September 27, 2019 4SC AG (4SC, FSE Prime Standard: VSC) reported the presentation of a number of new important scientific insights into the action of resminostat in cutaneous T-cell lymphoma (CTCL) at the EORTC Cutaneous Lymphoma Task Force Meeting in Athens, 26-28 September 2019 (Press release, 4SC, SEP 27, 2019, View Source [SID1234539858]).
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The majority of CTCL patients suffer from pruritus, which has a significant negative impact on the patient’s quality of life. In CTCL, severity of itching correlates with elevated levels of IL-31, a well described itch mediator in pruritic disorders. Resminostat treatment of CTCL cell lines reduces the level of IL-31 sustainably, indicating a potential to reduce itching in CTCL patients and thereby to improve their health-related quality of life. This will be further evaluated in the ongoing RESMAIN trial (NCT02953301) as key secondary endpoint and IL-31 levels will be measured as part of the biomarker program.
CTCL is characterized by malignant skin-homing T cells with an increasing bias towards the Th2 cell type during disease progression. Genome wide gene expression analysis after treatment of CTCL cell lines with resminostat shows a down regulation of skin homing receptors and of genes associated with disease progression. Interestingly, data presented at the EORTC-CLTF meeting demonstrate that resminostat up-regulates Th1 and down-regulates Th2 associated genes, thus favoring the beneficial Th1-phenotype. Taken together, these data provide insights into the transcriptional effects of resminostat in CTCL and strongly suggest that resminostat has the potential to delay or even prevent disease progression in CTCL.
Natural killer (NK) cells are potent effectors of the anti-tumoral innate defense. Preclinical data is presented demonstrating that resminostat positively promotes NK cell-mediated lysis of cancer cells, suggesting potential for resminostat in combination with opsonizing antibodies as a potential therapy in hematological cancer indications such as CTCL.
Susanne Danhauser-Riedl, M.D., Chief Medical Officer of 4SC, commented: "These data continue to illustrate the mode of action of resminostat in CTCL and underline its potential benefit for CTCL patients. We look forward to gathering more insights in 2020 from our RESMAIN pivotal study of resminostat in CTCL".