4SC – Resminostat and RESMAIN Study Update

• Independent Data Safety Monitoring Board recommends RESMAIN study to continue without modification following review of cumulative safety data from first 150 patients enrolled
• RESMAIN – a pivotal study to evaluate resminostat for maintenance treatment of patients with advanced-stage cutaneous T-cell lymphoma (CTCL) is increasing patient number in order to minimize the time to unblind the study, with top-line results now expected by the middle of 2021
• Yakult Honsha to discontinue Phase II study in biliary tract cancer in Japan, no monetary impact for 4SC

Planegg-Martinsried, Germany, 31 January 2020 – 4SC AG (4SC, FSE Prime Standard: VSC) today announced, that the Data Safety Monitoring Board (DSMB), an independent committee of clinical and drug safety experts, recommends continuation of the ongoing pivotal RESMAIN study without modification of the study protocol. Per the protocol’s pre-specified DSMB charter, a third DSMB meeting was scheduled recently to review cumulative unblinded safety data after 150 patients have been enrolled and completed at least one treatment cycle.  No further such reviews are planned.

The pivotal RESMAIN study, which is conducted as a multi-center, double blind, randomized, placebo-controlled study, evaluates resminostat for maintenance treatment of patients with advanced-stage cutaneous T-cell lymphoma (CTCL) who have achieved disease control with prior systemic therapy, at more than 50 clinical centers in 11 European countries, and 5 centers in Japan. The original study design estimated that 150 patients would be sufficient to see 125 events (i.e. disease progression) and unblind the study. Enrolment of 150 patients was reached in 2019, but having reviewed the number of events (blinded), 4SC elected to increase the total number of patients to 190 so as to minimize the additional time required to unblind the study.  Top-line results are now expected by the middle of 2021.

Susanne Danhauser-Riedl, M.D., Chief Medical Officer of 4SC, commented: “Safety and tolerability are key requirements for patients and physicians considering a drug especially for the treatment of patients in the maintenance setting. Advanced-stage CTCL patients usually respond to available treatment options but the duration of response is often short-lived and declines as the severity of the disease increases. The aim of a maintenance therapy and thus of our RESMAIN study is to make such remissions more durable, halting disease progression and improving the quality of life of patients.

We are encouraged by the positive outcome of the repeated independent DSMB safety reviews. So, we continue the trial with the aim of bringing resminostat to patients as quickly as possible.”

Biliary Tract Carcinoma

Yakult Honsha has informed 4SC of their decision to discontinue their Phase II study of resminostat in biliary tract cancer in Japan. This decision has no monetary implications for 4SC as this development program was funded entirely by Yakult and did not provide for development milestones for 4SC. 4SC was not intending to pursue this indication independently.

Related articles

27 September 2019, Key resminostat scientific data to be presented at EORTC-CLTF meeting in Athens

28 January 2019, 4SC’s pivotal RESMAIN study of resminostat in CTCL receives second positive safety review

20 November 2018, 4SC reaches significant milestone with enrollment of 100 patients in pivotal RESMAIN study of resminostat as CTCL maintenance therapy

28 June 2018, New data supports resminostat’s mechanism of action in CTCL maintenance therapy

27 March 2018, Yakult Honsha joins 4SC’s pivotal RESMAIN study of resminostat in CTCL – 4SC receives milestone payment

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 drug candidates in clinical development: resminostat and domatinostat.

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

About resminostat

Resminostat is an orally administered class I, IIb and IV histone deacetylase (HDAC) inhibitor that potentially offers an approach to treating different kinds of cancer. Resminostat demonstrated that it is well tolerated and can inhibit tumor growth and proliferation, cause tumor regression, and strengthen the body’s immune response to cancer.

Resminostat is currently being investigated in a pivotal study in cutaneous T-cell lymphoma (CTCL) by 4SC and its development partner Yakult Honsha in Japan.

About cutaneous T-cell lymphoma (CTCL)

CTCL is a rare disease with approximately 5,000 patients being newly diagnosed in Europe each year. The disease arises from malignant transformation of T-cells, a specialized subgroup of immune cells, primarily affects the skin, but may ultimately involve lymph nodes, blood and visceral organs.

Currently, CTCL is not curable and treatment options for advanced-stage CTCL are limited. Although patients respond to the available treatment options, the duration of response is often short-lived and declines as the severity of the disease increases. The key therapeutic challenge in advanced-stage CTCL is therefore to make remissions more durable by halting disease progression and improving patients quality of life.

About the RESMAIN study – resminostat for maintenance treatment of CTCL

The pivotal RESMAIN study is being conducted at more than 50 clinical centers in 11 European countries and Japan. It will include up to 190 patients who suffer from advanced-stage cutaneous T-cell lymphoma (CTCL) that have achieved disease control with systemic therapy. The patients are randomized 1:1 to receive either resminostat or placebo. Patients who experience disease progression – while being on placebo – will be offered resminostat in an open label treatment arm.

The primary goal of the study is to determine whether maintenance treatment with resminostat prolongs progression-free survival and the key secondary objective is to prolong the time to symptom worsening (itching). A comprehensive biomarker program is also included in the study to ensure vital knowledge about the biological background of resminostat treatment and CTCL is acquired. 4SC anticipates top-line data to be available around the middle of 2021.

The concept of maintenance therapy

The pivotal RESMAIN study is focused on patients with advanced-stage, incurable cutaneous T-cell lymphoma CTCL. Such patients suffer from painful and itchy skin lesions resulting in disfigurement and a severely impaired quality of life. Furthermore, lymph nodes, blood or visceral organs can be involved. None of the current therapeutic options achieve stable disease for long periods, with most patients progressing within six months (on average).

Resminostat is being evaluated as maintenance treatment – prolonging the period patients are stable and not progressing. Furthermore, recent preclinical data suggests that resminostat has the potential to alleviate the itching in CTCL patients, thereby additionally improving their quality of life.

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.