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4SC AG announces updated and progressive development program
4SC intends to raise new equity to fund accelerated development of 4SC’s lead drug candidates resminostat and 4SC-202 into pivotal studies and a first marketing authorization application, and 4SC-208 into clinical evaluation.
- Filing of a Marketing Authorisation Application (MAA) for resminostat in cutaneous T-cell lymphoma (CTCL) in Europe as soon as possible
- Advance resminostat into a pivotal study in advanced-stage liver cancer (hepatocellular cancer, HCC) in 2017
- Execute a fast to market strategy for 4SC-202 by advancing it into a first pivotal study in late 2018
- Complete formal preclinical development of 4SC-208 with aim of starting Phase I/II clinical testing in early 2019
Conference call to be hosted today, 16 May 2017, at 3 p.m. CEDT (9 a.m. EDT).
Planegg-Martinsried, Germany, 16 May 2017 – 4SC AG (4SC, FSE Prime Standard: VSC) today announced an updated development plan and intention to raise new capital to fund the further development of 4SC’s lead drug candidates resminostat, 4SC-202 and 4SC-208 until early 2020. Any final decision to conduct a capital raise will be announced by an additional ad hoc announcement.
Jason Loveridge, Ph.D., Chief Executive Officer of 4SC, explained the over-all strategy: “Since I joined 4SC in September 2016, we have been working to rationalize our portfolio of drug candidates and define a clear development strategy for our selected lead drug candidates resminostat, 4SC-202 and 4SC-208. Our main goal over the next 3 years is to create significant value for our shareholders by defining and funding accelerated routes to market for resminostat and 4SC-202, and to establish proof of concept for 4SC-208.
For resminostat, we are aiming to file a Marketing Authorisation Application (MAA) in CTCL in Europe as soon as possible after top-line results from our ongoing pivotal RESMAIN study, which are expected in early 2019. And additionally, we are working with potential partners to move resminostat into a pivotal study in HCC this year on the back of the Phase II data presented at 2017 Gastrointestinal Cancers Symposium in January.
For 4SC-202, we plan on initiating two Phase II studies in combination with checkpoint inhibitors starting in 2017 which will underpin a subsequent first pivotal study for 4SC-202 in an orphan indication such as Merkel-cell carcinoma (MCC, skin cancer) beginning in 2018. Finally, we will complete preclinical development of 4SC-208 with the aim of starting Phase I/II clinical testing in early 2019.
This is clearly an ambitious program with significant near term value drivers that with sufficient capital has the capacity to transform 4SC over the next 3 years.”
(1) Filing of a Marketing Authorisation Application (MAA) for resminostat in cutaneous T‑cell lymphoma (CTCL) in Europe as soon as possible
4SC is currently conducting the pivotal, European, multi-center, double blind, randomized, placebo-controlled RESMAIN study to evaluate resminostat for maintenance treatment of patients with advanced-stage CTCL who have achieved disease control with prior systemic therapy. Patient recruitment is advancing as planned and top-line results are expected in first half-year 2019. If the results are positive, 4SC will submit the data to the relevant regulatory agencies for market approval in Europe as soon as possible.
(2) Advance resminostat into a pivotal study in advanced-stage liver cancer (hepatocellular cancer, HCC) in 2017
4SC’s partner Yakult Honsha Co., Ltd. (Yakult Honsha) conducted a randomized 170 patient Phase I/II study of resminostat as a potential novel first-line treatment for patients with advanced-stage HCC in Japan and Korea. The study demonstrated a substantial overall survival benefit in a large subgroup comprised of 84 patients with a greater than median platelet count at study entry (the “platelet subgroup”).
During the discussions regarding further development of resminostat in the platelet subgroup, 4SC and Menarini Asia-Pacific Holdings Pte. Ltd. agreed to mutually terminate their licensing and development agreement for resminostat in the Asia-Pacific region excluding Japan. The rights to resminostat in Japan are held by Yakult Honsha and outside of Japan all respective rights now reside with 4SC.
4SC is currently negotiating terms for further development of resminostat in HCC including potentially a pivotal study with both Yakult Honsha as well as a small number of other potential partners.
(3) Execute a fast to market strategy for 4SC-202 by advancing it into a first pivotal study in late 2018
4SC-202 has been investigated in a Phase I study with 24 mostly heavily pretreated patients with advanced hematologic tumors, and has proven to be tolerated. Positive signs of anti-tumor efficacy were observed with one complete remission for 28 months and one partial responder for 8 months as well as disease control in 83% of patients. In preclinical experiments, 4SC-202 demonstrated anti-tumor effects and an ability to alter the tumor microenvironment particularly in combination with checkpoint inhibitors (e.g. anti-PD-L1 or anti-PD-1 antibodies).
Based on these data, in 2017, 4SC intends both to initiate a Phase II study in patients with advanced melanoma (skin cancer) who are refractory to treatment with checkpoint inhibitors and to support a further Phase II study in pre-treated patients with microsatellite-stable gastrointestinal cancers. In both studies 4SC-202 will be administered in combination with checkpoint inhibitors.
“We chose these settings and indications because they offer the opportunity to evaluate the combined safety and anti-tumor activity of 4SC-202 with approved PD-1 and PD-L1 inhibitors at different doses and, especially in melanoma, the ability to take serial biopsies before and during treatment,” explained Frank Hermann, M.D., Chief Development Officer of 4SC. “This setup has the potential to generate very important data on the tumor microenvironment and its modulation as well as to support our preclinical data and proposed synergistic mechanism of action of 4SC-202 in combination with checkpoint inhibitors. Results from these Phase II studies are expected in 2018 for melanoma and 2019 for microsatellite-stable gastrointestinal cancer and will underpin the advancement of 4SC-202 into a pivotal study in an orphan indication such as Merkel-cell carcinoma (MCC, skin cancer) beginning in 2018.”
(4) Complete formal preclinical development of 4SC-208 with aim of starting Phase I/II clinical testing in early 2019
4SC-208 is a small molecule specifically targeting two kinases crucial for Hedgehog/GLI signaling. Data from several preclinical in vivo models has established the efficacy of 4SC-208 in inhibiting this signaling pathway, which has emerged as a highly effective strategy in obstructing the tumorigenic capacity of cancer stem cells responsible for metastases and recurrence of tumors. 4SC-208 is expected to complete formal preclinical testing in 2018 and enter a Phase I/II clinical study immediately thereafter.
4SC’s Management will host a public English-language conference call today, 16 May 2017, at 3 p.m. CEDT (9 a.m. EDT) to provide more detail on the updated and progressive development plan. A presentation document supporting the conference call will be available at 4SC’s website. After the event, a replay can be accessed from there as well.
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Resminostat is an orally administered histone deacetylase (HDAC) inhibitor that potentially offers a novel approach to treating a wide variety of cancers, both as monotherapy and in combination therapy with other anti-cancer drugs. As an inhibitor that blocks HDAC classes I, IIB and IV, resminostat can potentially offer benefit to patients as it inhibits tumor growth and proliferation, causes tumor regression, and strengthens the body’s own immune response to cancer.
Resminostat has been shown to be well tolerated in patients with advanced cancers in Phase I studies. Its use in the treatment of cutaneous T-cell lymphoma (CTCL), Hodgkin’s lymphoma and liver, lung, colon, pancreatic and biliary tract cancers has been and is being investigated in further clinical studies. Initial positive efficacy results for resminostat in monotherapy were observed in patients with Hodgkin’s lymphoma and in combination with sorafenib in selected patients with advanced liver cancer (hepatocellular cancer, HCC).
4SC-202 is an orally administered small molecule for the treatment of cancer with a unique mode of action that inhibits both class I histone deacetylase proteins (HDAC 1, 2, 3) and the lysine-specific demethylase (LSD1) protein, which play significant roles in the regulation of signaling pathways in cancer cells.
4SC-202 has been investigated in a Phase I study with 24 mostly heavily pretreated patients with several types of highly advanced hematologic cancers, and has proven to be tolerated. Positive signs of anti-tumor efficacy were observed with one complete remission for 28 months and one partial responder for 8 months.
Data from preclinical investigations demonstrated that 4SC-202 strengthens the anti-tumor immune response, alters the tumor microenvironment and increases infiltration of immune cells into the tumor. Further preclinical investigations showed that the combination of 4SC-202 with checkpoint inhibitors resulted in better anti-tumor activity than treatment with checkpoint inhibitors alone, suggesting a very promising clinical development path for 4SC-202 in both refractory and non-responding patients to treatment with checkpoint inhibitors.
Data from several preclinical in vivo models has established the efficacy of 4SC-208 in inhibiting the Hedgehog/GLI signaling. Inhibition of this signaling pathway has emerged as a highly effective strategy in obstructing the tumorigenic capacity of cancer stem cells, as well as tumor development, proliferation and survival.
Inhibitors of Hedgehog signaling target the pathway upstream of the transcription factor GLI, whereas 4SC-208 inhibits at the level of GLI and is thus potentially able to avoid the tumor recurrence and relapse observed in response to currently available inhibitors.
4SC believes that 4SC-208 is a promising drug candidate and expects it to complete formal preclinical testing in 2018 and to enter into a Phase I/II clinical study immediately thereafter. Cancer indications that are particularly promising are those where resistance to therapies targeting the Hedgehog/GLI pathway are emerging, such as in basal cell carcinoma.
4SC AG is a clinical-stage biopharmaceutical company developing small-molecule drugs that can target key indications in cancer with high unmet medical needs. Such drugs are intended to provide patients with innovative treatment options that are more tolerable and efficacious than existing therapies and provide a better quality of life. 4SC’s core assets include resminostat, 4SC-202 and 4SC-208.
4SC’s pipeline is protected by a comprehensive portfolio of patents and comprises promising products that are in various stages of preclinical and clinical development. 4SC’s aim is 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. Founded in 1997, 4SC had 48 employees as of 31 March 2017. 4SC has been listed on the Prime Standard of the Frankfurt Stock Exchange since December 2005.
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