"The MERKLIN 2 study is addressing a very high unmet medical need in patients with advanced, unresectable MCC progressing on anti-PD-L1 or anti-PD-1 monotherapy. These patients don’t have any real viable treatment options, certainly no durable options and definitely do need better treatment in the future. The combination of domatinostat and avelumab has a clear and sound scientific rationale by targeting well described immune escape mechanisms in MCC by domatinostat to synergize with checkpoint inhibition and the MERKLIN 2 study is intended to investigate the efficacy and safety of this combination in these patients. Over 40 centers in Europe and the US are planned to enroll patients and I am pleased to present the Trial in Progress poster for MERKLIN 2 at this virtual ESMO meeting on behalf of my colleagues to give an update and make this important study visible for participation and potentially referrals of patients to the participating study sites. As MCC is an orphan disease and treatment options particularly in this patient population are very limited, this is of utmost importance," Alexander van Akkooi, MD Ph.D. from the Netherlands Cancer Institute (NKI) – Antoni van Leeuwenhoek Hospital (NKI-AVL), Amsterdam, the Netherlands and Global Coordinating Investigator of the MERKLIN 2 study says.

About domatinostat
Domatinostat is an orally administered small molecule class I selective HDAC inhibitor. It strengthens the body’s own anti-tumor immune response, influences the tumor and tumor microenvironment, making the tumor more visible to the immune system and facilitating the infiltration of immune cells into the tumor.

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. 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 from which initial data was presented at ESMO 2019. 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. DONIMI – a multicenter, investigator-sponsored phase 1b study, testing the combination of domatinostat, nivolumab, and ipilimumab, in high risk stage III melanoma in the neoadjuvant setting. MERKLIN 2 study is a Phase II clinical study evaluating domatinostat in combination with avelumab in patients with advanced MCC whose disease has progressed on anti-PD-(L)1 antibody therapy.

Avelumab Approved Indications in the US
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 and Medication Guide 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.