4SC – Clinical Study Presentations at the 31. German Conference of Skin Cancer (31. Hautkrebskongress)

Planegg-Martinsried, Germany, 8 September 2021 – 4SC AG (4SC, FSE Prime Standard: VSC) today announced, that PD Dr. Patrick Terheyden, from the Department of Dermatology, Allergology and Venerology, University Lübeck, Germany, will provide an update on the MERKLIN 1 and 2 studies at the 31. German Conference of Skin Cancer between the 8 and 11th September 2021.

About domatinostat

Domatinostat is an orally administered small molecule class I selective HDAC inhibitor. It strengthens the body’s own anti-tumor immune response. Domatinostat modulates the tumor and tumor microenvironment making it more visible to the immune system, susceptible to concomitant checkpoint inhibition, and facilitating the infiltration of immune cells into the tumor (Bretz et al., 2019). Domatinostat has been investigated in a Phase I study in 24 heavily pretreated patients with several types of advanced hematologic cancers and was well tolerated (Tresckow et al., 2019). Signs of single-agent anti-tumor efficacy were observed; with one complete remission and one partial responder. Besides its therapeutic potential as monotherapy, 4SC is focusing its development activities for domatinostat on 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 from which initial data was presented at ESMO 2019 (Hassel et al., abstract #5545) and at ASCO 2021 (Hassel et al., abstract #9545).A second Phase II study of domatinostat in combination with the anti-PD-L1 checkpoint inhibitor avelumab in patients with advanced-stage microsatellite-stable gastrointestinal cancer is currently being conducted by Prof. David Cunningham at The Royal Marsden NHS Foundation Trust in London, UK. In addition, in a collaboration with the Netherlands Cancer Institute in Amsterdam, the DONIMI Study, a multicenter, investigator-sponsored phase Ib study, is conducted testing the combination of domatinostat, nivolumab and ipilimumab in high risk stage III melanoma in the neoadjuvant setting. To advance this development program, 4SC has also signed a drug supply agreement with Merck KGaA for avelumab (anti-PD-L1 antibody) to conduct two Phase II clinical trials of domatinostat in combination with avelumab in advanced-stage Merkel cell carcinoma (MCC) patients progressing on previous anti-PD-(L)1 monotherapy (MERKLIN 2) and in metastatic treatment-naïve patients (MERKLIN 1).

Avelumab Approved Indications

Avelumab (BAVENCIO®) is indicated in the US for the maintenance treatment of patients with locally advanced or metastatic urothelial carcinoma (UC) that has not progressed with first-line platinum-containing chemotherapy. BAVENCIO is also indicated for the treatment of patients with locally advanced or metastatic UC who have disease progression during or following platinum-containing chemotherapy, or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

Avelumab in combination with axitinib is approved in the US for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

In the US, the FDA granted accelerated approval for BAVENCIO for the treatment of adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials.

Avelumab Important Safety Information from the US FDA-Approved Label

The warnings and precautions for avelumab (BAVENCIO®) include immune-mediated adverse reactions (such as pneumonitis and hepatitis [including fatal cases], colitis, endocrinopathies, nephritis, and other immune-mediated adverse reactions as a single agent or in combination with axitinib [which can be severe and have included fatal cases]), infusion-related reactions, hepatotoxicity in combination with axitinib, major adverse cardiovascular events (MACE) in combination with axitinib [which can be severe and have included fatal cases], and embryo-fetal toxicity.

Common adverse reactions (reported in at least 20% of patients) in patients treated with BAVENCIO® monotherapy include fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reaction peripheral edema, decreased appetite, urinary tract infection and rash. Common adverse reactions (reported in at least 20% of patients) in patients receiving BAVENCIO® in combination with axitinib include diarrhea, fatigue, hypertension, musculoskeletal pain, nausea, mucositis, palmar-plantar erythrodysesthesia, dysphonia, decreased appetite, hypothyroidism, rash, hepatotoxicity, cough, dyspnea, abdominal pain and headache. Grade 3-4 hematology laboratory value abnormalities reported in at least 10% of patients with Merkel cell carcinoma treated with BAVENCIO® monotherapy include lymphopenia; in patients receiving BAVENCIO® in combination with axitinib, grade 3-4 clinical chemistry abnormalities include blood triglyceride increased and lipase increased.

For full US Prescribing Information (https://www.emdserono.com/content/dam/web/corporate/non-images/country-specifics/us/pi/bavencio-pi.pdf?Version=) and Medication Guide (http://www.emdserono.com/bavenciomedicationguide) for BAVENCIO®, please see http://www.BAVENCIO.com.

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.