4SC AG: First Patient Enrolled in MERKLIN 2 Study

4SC AG (4SC, FSE Prime Standard: VSC) today announced that the first patient has been enrolled in the MERKLIN 2 study investigating the combination of 4SC’s selective HDAC class I inhibitor domatinostat and avelumab in Merkel cell carcinoma (MCC).

MCC is an orphan, highly immunogenic type of non-melanoma skin cancer. In 2017, avelumab (BAVENCIO®), which is co-developed and co-commercialized by Merck KGaA, Darmstadt, Germany and Pfizer Inc., was the first anti-PD-(L)1 antibody approved in both the EU and US for metastatic MCC. Although anti-PD-(L)1 antibodies are now standard of care in metastatic MCC, around half of all such patients still have progressive disease, and currently lack any effective therapeutic options and suffer from high mortality, outlining the high unmet medical need.

"There is a very strong preclinical and scientific rationale to combine domatinostat and avelumab in patients with advanced MCC progressing on anti-PD-L1 or anti-PD1 monotherapy. To target well described immune escape mechanisms in MCC by domatinostat to make patients susceptible for checkpoint inhibition is clearly promising. It is an important milestone having now enrolled the first patient into MERKLIN 2 and being able to offer these patients with very limited treatment options the opportunity to participate.", 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 mentions.

Jason Loveridge, Ph.D., CEO of 4SC, says: "We are delighted to enroll the first patient in our MERKLIN 2 study where we intend to evaluate domatinostat in combination with avelumab in patients with MCC that progressed on treatment with checkpoint inhibitors. We are absolutely pleased to know the broad support of the MERKLIN 2 Investigators to address this high unmet medical need and to have worldwide leading clinical experts in MCC participating in the study. In addition, it is a great honor being able to conduct this study under the clinical trial collaboration and supply agreement with Merck KGaA, Darmstadt, Germany and Pfizer for avelumab supply."

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. And in collaboration with the Netherlands Cancer Institute in Amsterdam, the DONIMI Study, 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.

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 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.