On 21 March 2017 4SC AG (4SC, FSE Prime Standard: VSC) reported that it will present two posters supporting the continued development of its product candidate 4SC-202, an epigenetic modulator with a unique mechanism of action that inhibits both the lysine-specific demethylase (LSD1) protein and class I histone deacetylase proteins (HDAC1, 2, 3), at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, being held on 1-5 April 2017 in Washington, D.C., USA (Press release, 4SC, MAR 21, 2017, View Source [SID1234518599]). Schedule your 30 min Free 1stOncology Demo! Both posters will be published on 4SC’s website on 3 and 4 April 2017, respectively.
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4SC-202 plus checkpoint inhibition – boosting the immune system to fight cancer
"In the first set of experiments, we investigated the anti-tumor activity and mode of action of 4SC-202, both as single agent and in combination with anti-PD1 and anti-PD-L1 antibodies, both checkpoint inhibitors, in immunocompetent and immunocompromised mice. 4SC-202 showed anti-tumor activity alone and synergized with checkpoint inhibition by stimulating the immune system and increasing the number of cancer-killing cytotoxic T cells in the tumor microenvironment. Most importantly, this was achieved without harming the viability of the anti-tumor T cells, which differentiates 4SC-202 from other HDAC inhibitors," summarized Frank Hermann, M.D., Chief Development Officer of 4SC.
"These promising preclinical results build a rationale for further clinical development of 4SC-202. As we see highly synergistic effects of 4SC-202 in combination with checkpoint inhibitors, we should investigate the addition of 4SC-202 in cancer patients who are not responding to treatment with checkpoint inhibitors alone. In these patients, 4SC-202 might help to reactivate the immune system to fight the cancer."
Abstract #2632 / Poster #21: 4SC-202 induces inflamed tumor microenvironment, strongly enhances tumor infiltration with cytotoxic T cells and primes tumors for anti-PD-1/PD-L1 therapy
Date: Monday, 3 April 2017
Time: 1 – 5 p.m. EDT
Location: Section 25
4SC-202 – a potentially interesting player in acute myeloid leukemia (AML)
"In the second set of experiments we investigated a different capability of 4SC-202: the ability to induce differentiation in acute myeloid leukemia (AML) cells, which is a therapeutic approach already in use to treat that disease. We evaluated the anti-tumor activity of 4SC-202 alone and in combination with various cytokines to identify a suitable combination," said Roland Baumgartner, Ph.D., Chief Scientific Officer of 4SC.
"Treatment with 4SC-202 alone induced differentiation in AML cells. In combination with the cytokine interferon-γ (IFN-γ), 4SC-202 induced an enhanced tumor-specific T-cell response that can act against residual malignant AML cells which additionally highlights the potential of 4SC-202 to boost anti-tumor immunity."
Abstract #3088 / Poster #5: Combination of 4SC-202 and IFN-γ restores mature APC phenotype in AML cells
Date: Tuesday, 4 April 2017
Time: 8 a.m. – 12 p.m. EDT
Location: Section 3
Related articles
2 June 2016, 4SC at ASCO (Free ASCO Whitepaper): 4SC 202 and checkpoint inhibitors – strong partners in cancer treatment
21 March 2016, Epigenetic compound 4SC-202 strengthens endogenous immune response to cancer
Further information
About 4SC-202
4SC-202 is an orally administered small molecule for the treatment of cancer. 4SC-202 is an epigenetic modulator with a unique mechanism of action that inhibits both the lysine-specific demethylase (LSD1) protein and class I histone deacetylase proteins (HDAC1, 2, 3), which play significant roles in the regulation of signaling pathways in degenerated cancer cells.
4SC-202 has been investigated in a Phase I study with 24 intensively pretreated patients with several types of highly advanced hematologic cancers, and has proven to be tolerated. Positive signs of anti-tumor efficacy were observed with one complete remission for 28 months and one partial responder for 8 months.
Data from preclinical investigations showed that 4SC-202 strengthens the anti-tumor immune response. Treatment with 4SC-202 alters the tumor microenvironment and increases infiltration of immune cells into the tumor. In June 2016, further preclinical investigations showed that the combination of 4SC-202 with checkpoint inhibitors resulted in better anti-tumor activity than treatment with checkpoint inhibitors alone, suggesting a very promising clinical development path for 4SC-202 in both refractory and non-responding patients to treatment with checkpoint inhibitors.
About checkpoint inhibitors
The human immune system is capable of self-regulation via a wide variety of mechanisms to prevent excessive or misdirected defensive reactions. Tumors exploit these immune system "checkpoints" to switch off the immune response that specifically targets them. This is where checkpoint inhibitors are effective: they inhibit the signaling pathways to "release the brakes" on the immune cells and enable them to attack the cancerous tissue again.
Examples of checkpoint inhibitors that have returned promising data after investigation in clinical trials worldwide include drugs that block the PD-1 (Programmed Death-1) receptor on the surface of immune cells. The PD-1 receptor interacts with its ligands PD-L1 or PD-L2 on the surface of cancer cells to prevent the immune cells from attacking the tumor. With the PD-1 receptor or its ligand PD-L1 blocked, cancer cells can no longer escape the immune response.