4SC-202 – a promising combination partner for cancer treatment

Two poster presentations at the AACR Annual Meeting, 1-5 April 2017, Washington, D.C., USA

Planegg-Martinsried, Germany, 21 March 2017 – 4SC AG (4SC, FSE Prime Standard: VSC) today announced 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) Annual Meeting, being held on 1-5 April 2017 in Washington, D.C., USA.

Both posters will be published on 4SC’s website on 3 and 4 April 2017, respectively.

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: 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.


About epigenetic cancer therapy

Epigenetic changes modify the activity of genes, but not the genetic code of DNA itself, causing activation or silencing of genes. This mechanism enables differentiated cells such as those in the lungs, nerves or skin to serve very different functions despite containing identical genetic code.

Epigenetic alterations are as important as genetic mutations in a cell’s transformation to cancer; and their manipulation holds great promise for improving cancer therapy. Epigenetic compounds such as 4SC’s resminostat and 4SC-202 have the potential to convert these malignant epigenetic alterations back to a normal or non-malignant state. For example, treatment with epigenetic cancer compounds interrupts or combats the mechanism that is responsible for the onset of cancer, making cancer cells visible to the body’s own immune system or rendering them more responsive to immuno-oncological treatment.

Epigenetic therapeutics is considered as a future growth market in the field of oncology based on its significant promise as both a monotherapy and in combined approaches with immuno-oncology drugs and other therapeutic agents. In an October 2015 report by business information publisher Grand View Research, the worldwide epigenetics market was projected to generate revenues of US-$16 billion in 2022, up from US-$ 4 billion in 2014.


About 4SC

4SC is a clinical-stage biopharmaceutical company developing small-molecule drugs that can target key indications in cancer with high unmet medical needs through epigenetic mechanisms. Such drugs are intended to provide patients with innovative treatment options that are more tolerable and efficacious than existing therapies and provide a better quality of life.

4SC’s pipeline is protected by a comprehensive portfolio of patents and comprises promising products that are in various stages of preclinical and clinical development. 4SC’s aim is to generate future growth and enhance its enterprise value by entering into partnerships with pharmaceutical and biotech companies. Founded in 1997, 4SC had 49 employees as of 31 December 2016. 4SC has been listed on the Prime Standard of the Frankfurt Stock Exchange since December 2005.

Forward-looking information

Information set forth in this press release contains forward-looking statements, which involve a number of risks and uncertainties. The forward-looking statements contained herein represent the judgement of 4SC as of the date of this press release. Such forward-looking statements are neither promises nor guarantees, but are subject to a variety of risks and uncertainties, many of which are beyond 4SC’s control, and which could cause actual results to differ materially from those contemplated in these forward-looking statements. 4SC expressly disclaims any obligation or undertaking to release any updates or revisions to any such statements to reflect any change in its expectations or any change in events, conditions or circumstances on which any such statement is based.

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