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Epigenetic compound 4SC-202 strengthens endogenous immune response to cancer
Promising research data open up new horizons for the clinical development of the epigenetic oncology compound 4SC-202
4SC-202 uses epigenetic mechanisms to attack cancer tissue, ensuring that genes silenced in cancer cells can once again be read or that excessively active regions can be downregulated. Malfunctions in genetic activity caused by cancer cells can e.g. prevent the immune system from attacking the tumor.
"In preclinical investigations, treatment with 4SC-202 caused cancer tissue to become visible to the body's own immune cells," explains Dr Daniel Vitt, 4SC's Chief Development Officer & Chief Scientific Officer. "Immune cells in the immediate vicinity of the tumors were no longer suppressed but strengthened, and therefore capable of entering and attacking these tumors. In mice treated with 4SC-202, the growth rate of cancer tissue was significantly slower than in the control group." These observations were substantiated by further experiments in cell cultures. Unlike comparable medications, 4SC-202 targets and attacks cancer cells while leaving immune cells largely untouched.
4SC's CEO Enno Spillner explains the significance of these data: "Our data confirm this promising epigenetic substance's great potential, which was first demonstrated during last year's successfully completed Phase I TOPAS trial. In this study, 4SC-202 proved to be safe and well-tolerated in patients with advanced hematologic cancer. The new immunological data we have collected now offer additional options for the clinical development of 4SC-202." Key treatment approaches now being considered include those for patients with hematological tumors or small-cell lung cancer, in combination with established immunotherapeutic treatments.
Dr Svetlana Hamm, Head of Biology at 4SC, will present the new immunological data on 4SC-202 in a poster session at the 3rd Immunotherapy of Cancer conference in Munich, Germany, which will be held from 21-23 March at Klinikum Rechts der Isar, Lecture Hall A, Ismaninger Strasse 22.
Administered as a tablet, 4SC-202 is an epigenetic oncology compound with a unique therapeutic profile. In the clinical Phase I TOPAS trial, which ran until March 2015, 4SC-202 was studied in 24 patients with advanced hematological cancer. The compound proved to be safe and well-tolerated. The patient's condition stabilized for half of the patients in the trial, with cancer tissue shrinking in one study participant, and one study participant experiencing complete tumor regression.
4SC-202 works as a selective inhibitor of LSD1 and HDAC1, 2 and 3. LSD1 (lysine-specific demethylase) and HDACs (histone deacetylases) are epigenetically active enzymes, one of whose effects is to alter the histones around which the DNA in our cells is wound. Accordingly, LSD1 and HDACs can promote or suppress the expression of specific genes. In a number of cancers, the activity of LSD1 and HDAC is deregulated but can be returned to normal by treatment with 4SC-202.
One effect of 4SC-202's epigenetic mechanisms of action is to block several key signaling pathways in cancer cells involved in cancer genesis and metastasis formation. 4SC-202 also strengthens the endogenous immune response to cancer tissue. 4SC-202 not only improves the visibility of cancer cells for the immune system by upregulating antigens associated with tumors, but also downregulates specific enzymes that prevent the immune cells from combating cancer cells effectively.
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.
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