4SC and Netherlands Cancer Institute Collaborate on Clinical Evaluation of Domatinostat in the Neoadjuvant Setting in Melanoma

• 40 patient Phase Ib study to start in Q4, 2019

 Planegg-Martinsried, Germany, 16 October 2019 – 4SC AG (4SC, FSE Prime Standard: VSC) today announced a collaboration with the Netherlands Cancer Institute (Stichting Het Nederlands Kanker Instituut (NKI) – Antoni van Leeuwenhoek Ziekenhuis) in Amsterdam to evaluate domatinostat in combination with checkpoint blockade in a “Multicenter Phase 1b Study testing the Neoadjuvant Combination of Domatinostat, Nivolumab, and Ipilimumab, in RECIST 1.1-measurable Stage III Cutaneous or Unknown Primary Melanoma – DONIMI”.

Immunotherapy, and particularly checkpoint inhibitors like anti-PD-1 (e.g. Nivolumab) and anti-CTLA4 (Ipilimumab), are increasingly investigated not only in the advanced unresectable or metastatic setting but also in earlier stages of disease. The rationale for such treatment is to activate the immune system before resection of the tumor to generate an immune memory and prevent recurrence of the disease. On the basis of some encouraging data published by the International Neoadjuvant Melanoma Consortium (INMC; https://melanoma-inc.org/), innovative combination approaches will now be tested to optimize the treatment in a more personalized manner where domatinostat is a promising combination partner.

Jason Loveridge, Ph.D., CEO of 4SC: “It is getting clearer and clearer that immunotherapy for cancer is most effective when used early in disease progression and we believe the neoadjuvant setting offers a great potential for protecting patients from recurrence of their malignancy after resection, potentially leading to a much higher number of cured patients with resectable, high-risk melanoma. Prof. Blank and his collaborators within the INMC have already made remarkable progress in this highly innovative field in melanoma and the NKI is a worldwide leading cancer center in the treatment of melanoma and other indications in the neoadjuvant setting. We are grateful entering such collaboration with the NKI and looking forward to the initiation of the DONIMI study in the near future.”

Prof. Dr. Christian Blank, NKI: “It is exciting to see what we have achieved with neoadjuvant immunotherapy in melanoma within the INMC during the last few years. However there´s still a way to go to implement a standard neoadjuvant treatment in melanoma.  Additional combination approaches to modulate the tumor microenvironment and the patients´ immune system remains a priority so as to optimize and personalize treatment for patients with melanoma, and potentially impact the treatment of patients with other cancers. For example, we do not know yet which patients require double neoadjuvant checkpoint inhibition and who can be treated with neoadjuvant PD-1 blockade alone. Based on preclinical and early clinical data, epigenetic modulation with domatinostat in combination with checkpoint blockade might be a promising approach in the neoadjuvant setting. In the DONIMI study, Domatinostat will be one of the first compounds tested in a personalized neoadjuvant combination trial implemented by INMC researchers from Sydney and Amsterdam. We are much looking forward to enroll the first patients later this year.“

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15 August 2018, FDA approves IND application for domatinostat (4SC-202) in melanoma

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. 4SC’s pipeline is protected by a comprehensive portfolio of patents and currently comprises two key drug candidates in various stages of clinical development: resminostat and domatinostat (4SC-202).

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 30 June 2019 and is listed on the Prime Standard of the Frankfurt Stock Exchange (FSE Prime Standard: VSC; ISIN: DE000A14KL72).

About The Netherlands Cancer Institute

The Netherlands Cancer Institute (NKI), including the Antoni van Leeuwenhoek Hospital, is the only dedicated Comprehensive Cancer Centre in the Netherlands and has been at the international forefront of cancer care and research for more than a century. In 2017, the European Academy of Cancer Sciences designated the NKI a Comprehensive Cancer Centre of Excellence for translational research. The NKI maintains an important role as a national and international centre of scientific and clinical expertise, development and training. Research focus areas are molecular biology, immunotherapy, personalized medicine, image-guided interventions and cancer survivorship.

Nowadays, The Netherlands Cancer Institute accommodates approximately 650 scientists and scientific support personnel. The Antoni van Leeuwenhoek Hospital has 222 medical specialists, 212 beds, an out-patients clinic with around 134,000 visits, 12 operating theatres and 12 irradiation units for radiotherapy.

About domatinostat

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 (SENSITIZE) and data from the first part of the study was presented at ESMO in Barcelona. 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 being conducted by Prof. David Cunningham of The Royal Marsden NHS Foundation Trust, London, UK (EMERGE).

4SC also plans to advance domatinostat into a number of studies in combination with a checkpoint inhibitor in PD-(L)1 refractory patients with advanced Merkel-cell carcinoma (MERKLIN).

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.