4SC at AACR: Broadened clinical options for 4SC-202

• Promising new preclinical data on 4SC-202 in double and triple combinations with checkpoint inhibitors
• Poster presentation at the AACR Annual Meeting, 14-18 April 2018, Chicago, USA

Planegg-Martinsried, Germany, 17 April 2018 – 4SC AG (4SC, FSE Prime Standard: VSC) today announced that it will present a poster on preclinical data supporting the combination of 4SC-202 and immunotherapeutic agents in cancer therapy at the American Association for Cancer Research (AACR) Annual Meeting being held on 14-18 April 2018 in Chicago, USA. The poster will be available on 4SC’s website after the presentation.

Scientific details – 4SC-202 in double and triple combinations with checkpoint inhibitors

4SC investigated the anti-tumor activity of the combination of 4SC-202, an orally available small molecule inhibitor targeting class I histone deacetylases, with several therapeutic antibodies which stimulate an immune response by blocking immune checkpoints in tumor models. A clinically equivalent dosage regimen was used to ensure relevance to the clinical situation.

Whereas the response rate to the checkpoint inhibitors alone was low, reflecting the refractory clinical situation in patients who do not respond to treatment, the combination of 4SC-202 with an antibody against CD137 resulted in 80% tumor regression and the combination with PD-1 blockade resulted in significantly longer survival and durable complete responses in more than 80% of the treated mice. The triple combination of 4SC-202 with two different checkpoint inhibitors (antibodies against PD-1 and LAG3) was even superior to the tested mono-therapies and double combinations.

Clinical development strategy for 4SC-202

Frank Hermann, M.D., Chief Development Officer of 4SC, commented: “We already knew that 4SC-202 strengthened the body’s own anti-tumor immune response, especially if combined with checkpoint inhibitors. In these most recent preclinical experiments, we observed increased tumor control, durable responses and increased survival of mice treated with 4SC-202 in combination with several classes of immuno-therapeutics, indicating the general immunomodulatory capacity of 4SC-202.

Currently, we are investigating the combination of 4SC-202 with a checkpoint inhibitor in a clinical trial in advanced stage melanoma patients and a second trial of 4SC-202 in combination with another checkpoint inhibitor in gastrointestinal cancers is to be initiated soon. Taking the data from these two studies, we aim to initiate a pivotal clinical trial with 4SC‑202 as soon as possible thereafter in the skin cancer Merkel-cell carcinoma.

Based on these promising preclinical results, we are evaluating further clinical trials in which we would combine 4SC-202 with checkpoint inhibitors and other immunotherapeutic agents.”

Abstract #4722 / Poster #25: 4SC-202 primes tumor microenvironment for treatment with cancer immunotherapy

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About 4SC-202

4SC-202 is an orally administered small molecule with a unique mode of action that was designed to strengthen the body’s own anti-tumor immune response, open the tumor microenvironment and encourage infiltration of immune cells into the tumor.

4SC-202 has been investigated in a Phase I study with 24 heavily pretreated patients with several types of highly advanced hematologic cancers and was proven to be well tolerated. Positive signs of anti-tumor efficacy were 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 4SC-202’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 4SC-202 in combination with the anti-PD-1 checkpoint inhibitor pembrolizumab in patients with advanced-stage melanoma. A second Phase II study of 4SC-202 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 4SC-202 into a pivotal study in combination with a checkpoint inhibitor in PD-(L)1 refractory patients with advanced Merkel cell carcinoma (MCC).

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 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. 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 currently comprises three key drug candidates in various stages of preclinical and clinical development: resminostat, 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 48 employees as of 31 December 2017 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.