4SC AG: Domatinostat plus chemotherapy – Overcoming drug resistance

  • Domatinostat (4SC-202) renders cancer cell lines more susceptible to chemotherapy treatment
  • Poster presentation at the SIC Annual Meeting, 19-22 September 2018, Milan, Italy


Planegg-Martinsried, Germany, 20 September 2018 – Preclinical data showing that a combination of 4SC AG’s (4SC, FSE Prime Standard: VSC) domatinostat (4SC-202) with chemotherapy increased inhibition of cell growth when compared to treatment with either alone will be presented at the 60th Annual Meeting of the Italian Cancer Society (SIC), held on 19-22 September 2018 in Milan, by 4SC’s collaborator Alfredo Budillon, M.D., Ph.D., Head of the Experimental Pharmacology Unit in the Department of Research at the Istituto Nazionale Tumori IRCCS “Fondazione Pascale” in Naples, Italy. The poster will be available on 4SC’s website after the presentation.

Alfredo Budillon summarized the experiments: “In order to improve therapeutic efficacy of conventional treatment, we tested potential combination strategies of the class I specific histone deacetylase inhibitor domatinostat plus chemotherapy regimens such as gemicitabine/paclitaxel or fluoropyrimidines/irinotecan (FOLFIRI) in several pancreatic cancer models. We already observed anti-tumoral effects on the cancer cell lines such as inhibition of tumor growth and induction of cell death using domatinostat alone. By combining domatinostat with chemotherapy regimens we saw synergistically increased inhibition of cell growth compared to single treatment with either domatinostat or chemotherapy, producing best results when domatinostat was added 24 hours prior to chemotherapy.”

4SC is currently evaluating domatinostat in combination with the checkpoint inhibitor pembrolizumab, a form of immunotherapy, in the Phase Ib/II clinical SENSITIZE study in advanced melanoma patients. Earlier this year, 4SC published preclinical data which demonstrated increased tumor control, durable responses and increased survival of mice treated with domatinostat in combination with several classes of immuno-therapeutics.

Frank Hermann, M.D., Chief Development Officer of 4SC, said: “We thank our collaborators for their enthusiasm and energy in their research work with domatinostat. The addition of this new preclinical data on the combination of domatinostat with several forms of chemotherapy underlines domatinostat’s potential to be a promising combination partner, for example to overcome drug resistance to different treatment classes in cancer. Based on these promising results, we are evaluating further clinical trials of domatinostat in various combinations.”


Abstract #E3: 4SC-202 (domatinostat), a novel histone deacetylase inhibitor, improves chemotherapy efficacy and overcomes drug resistance in pancreatic cancer models.

Date: 20 and 21 September 2018
Time: 12:00 – 13:00
Location: Poster Viewing area; Università degli Studi di Milano

Related articles

15 August 2018, 4SC AG: FDA approves IND application for domatinostat (4SC-202) in melanoma

31 July 2018, First patient enrolled in 2nd dose cohort of Phase Ib/II study SENSITIZE of domatinostat (4SC-202) + pembrolizumab in melanoma

17 April 2018, 4SC at AACR: Broadened clinical options for 4SC-202

About domatinostat (4SC-202)

Domatinostat is an orally administered small molecule Class I selective HDAC inhibitor with a unique mode of action that was designed to strengthen the body’s own anti-tumor immune response. Domatinostat also influences the tumor microenvironment facilitating infiltration of immune cells into the tumor and making it more visible to the immune system.

Domatinostat has been investigated in a Phase I study with 24 heavily pretreated patients with several types of advanced hematologic cancers and was well tolerated. Positive signs of anti-tumor efficacy were also observed; with one complete remission (28 months) and one partial responder (8 months).

In addition to its therapeutic potential in cancer monotherapy, 4SC is evaluating domatinostat’s capacity as a partner in combination therapies, specifically in the immuno-oncology area. In this respect, 4SC initiated a Phase Ib/II study of domatinostat in combination with the anti-PD-1 checkpoint inhibitor pembrolizumab in patients with advanced-stage melanoma. A second Phase II study of domatinostat in combination with the anti-PD-L1 checkpoint inhibitor avelumab, which will be conducted by an academic partner in gastrointestinal cancers, is expected to start soon.

As soon as results from the aforementioned trials will be available, 4SC plans to advance domatinostat into a pivotal study in combination with a checkpoint inhibitor in PD-(L)1 refractory patients with advanced Merkel cell carcinoma (MCC).

About 4SC

4SC AG is a clinical-stage biopharmaceutical company developing small-molecule drugs that can target key indications in cancer with high unmet medical needs. 4SC’s pipeline is protected by a comprehensive portfolio of patents and currently comprises three key drug candidates in various stages of preclinical and clinical development: resminostat, domatinostat (4SC-202) and 4SC-208.

4SC aims to generate future growth and enhance its enterprise value by entering into partnerships with pharmaceutical and biotech companies and/or the eventual marketing and sales of approved drugs in select territories by 4SC itself.

4SC is headquartered in Planegg-Martinsried near Munich, Germany. The Company had 45 employees as of 30 June 2018 and is listed on the Prime Standard of the Frankfurt Stock Exchange (FSE Prime Standard: VSC; ISIN: DE000A14KL72).

Forward-looking information

Information set forth in this press release contains forward-looking statements, which involve 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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