DGAP-News: 4SC AG: Positive safety review of 4SC's Phase Ib/II SENSITIZE study of domatinostat (4SC-202) + pembrolizumab in melanoma

Positive safety review of 4SC's Phase Ib/II SENSITIZE study of domatinostat (4SC-202) + pembrolizumab in melanoma

• Safety Review Committee (SRC) examined data from first dose cohort
• SRC recommends SENSITIZE to continue with second dose cohort
• Data from the first two of three cohorts expected in H2 2018

Planegg-Martinsried, Germany, 3 July 2018 - 4SC AG (4SC, FSE Prime Standard: VSC) today announced, that the Safety Review Committee (SRC) consisting of clinical and drug safety experts evaluated the safety data from the first dose cohort and recommended continuation with the second dose cohort in the ongoing Phase Ib/II SENSITIZE study. Full data analysis of the first patient cohort will be published at an upcoming conference.

The SENSITIZE study is enrolling up to 40 patients suffering from unresectable advanced-stage cutaneous melanoma who are refractory or non-responding to prior treatment with anti-PD-1 antibodies (checkpoint inhibitors). In the first part of the study, three patient cohorts will be treated at three different dose levels of domatinostat in combination with pembrolizumab. In the second part, additional patients will be treated with the recommended dosing regimen defined in the first dose-finding part of the study. Data from the first two dose cohorts are expected to be published during H2 2018, with topline results of the complete study in H1 2019.

Susanne Danhauser-Riedl, M.D., Chief Medical Officer of 4SC, commented: "Safety and tolerability are key requirements for patients and physicians considering a drug. We are encouraged by the positive outcome of the first safety review and are looking forward to enrolling patients into the second dose cohort. We will continue to execute on our clinical development plan for domatinostat, which is intended to lead to the initiation of a pivotal trial in 2019."

- Press release ends -

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6 November 2017, First patient enrolled in Phase Ib/II study SENSITIZE of 4SC-202 in melanoma

Further information

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 the SENSITIZE study - Domatinostat (4SC-202) + pembrolizumab for treatment of melanoma

The SENSITIZE Phase Ib/II study (ClinicalTrials.gov identifier: NCT03278665) was opened for recruitment from 25 September 2017 and is conducted at 6 certified skin cancer centers in Germany. It will enroll up to 40 patients suffering from unresectable advanced-stage cutaneous melanoma who are refractory or non-responding to prior treatment with anti-PD-1 antibodies (checkpoint inhibitors). In the first part of the study, 3 cohorts will be treated at different dose levels of domatinostat in combination with pembrolizumab. In the second part, additional patients will be treated with the recommended dosing regimen defined in the first part of the study.

The primary goal of the study is to determine the safety and tolerability of domatinostat in combination with pembrolizumab and key secondary endpoints aim to assess the anti-tumor activity of the combination treatment. Additionally, the study will investigate changes in key immunological biomarkers to better understand how domatinostat renders patients more susceptible to treatment with checkpoint inhibitors. 4SC anticipates top-line data to be available in 2018.

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, 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 47 employees as of 31 March 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.

Contact

Anna Niedl, Ph.D., CIRO
Corporate Communications & Investor Relations
anna.niedl@4sc.com
+49 89 700763-66