As a result of this review the management of 4SC has decided on a number of modifications as follows: to support the decision of the Netherlands National Cancer Institute to increase the study size of DONIMI phase Ib to up to 50 patients in total and thereby increase the robustness of the results recently presented at ESMO in September 2021; complete the phase Ib part of the SENSITIZE study; continue the MERKLIN 2, TURANDOT and EMERGE studies as planned; and to suspend further activities on the MERKLIN 1 study, which is yet to enroll its first patient.

Jason Loveridge, Ph.D., CEO of 4SC commented: "The coronavirus pandemic has had a significant impact on the progress of our clinical programs and we needed to re-evaluate our strategic priorities in order to best utilize shareholders’ funds. On this occasion we have decided our development strategy is best served by focusing our resources exclusively on checkpoint inhibitor naïve patients in curative, resectable stages of disease, through DONIMI and TURANDOT, and on patients with metastatic relapsed/refractory disease that have progressed on previous therapy – in SENSITIZE, MERKLIN 2 and EMERGE. As always, we will update investors on our progress and continue to expect to publish new clinical data for domatinostat in 2022 as already outlined in earlier communications."

About domatinostat

Domatinostat (http://www.4sc.com/product-pipeline/4sc-202/) 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 updated data at ASCO 2021.

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 and the TURANDOT Study are conducted. The DONIMI Study is a multicenter, investigator-sponsored phase Ib study testing the combination of domatinostat, nivolumab and ipilimumab in high-risk stage III melanoma in the neoadjuvant setting. The TURANDOT Study is a multicenter, investigator-sponsored phase Ib study testing the combination of domatinostat, nivolumab and ipilimumab in resectable stage II-III urothelial cancer in the neoadjuvant setting.

To advance this development program, 4SC has also signed a drug supply agreement with Merck KGaA, Darmstadt, Germany and Pfizer Inc. for avelumab (anti-PD-L1 antibody), to conduct phase II clinical trials of domatinostat in combination with avelumab in advanced-stage Merkel cell carcinoma (MCC).

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.