4SC Announces Initial Phase II Data from the SAPHIRE Study with Resminostat at the 8th International Symposium on Hodgkin Lymphoma

(PresseBox) (Planegg-Martinsried, ) 4SC AG (Frankfurt, Prime Standard: VSC), a drug discovery and development company focused on autoimmune and cancer indications, announces the presentation of Phase II data from Hodgkin Lymphoma patients treated in the 1st Simon Stage cohort of the ongoing SAPHIRE study with resminostat (4SC-201), an oral pan-histone deacetylase (HDAC) inhibitor, at the 8th International Symposium on Hodgkin Lymphoma in Cologne, Germany.

The oral presentation will be given by the lead investigator of the SAPHIRE study, Prof Dr Jan Walewski of the Marie-Sk?odowska-Curie Memorial Institute in Warsaw, Poland. It highlights initial safety and tolerability as well as efficacy data from the first 18 patients with relapsed or refractory Hodgkin Lymphoma in this study.

Daily oral application of 600 mg resminostat for 5 consecutive days per 2-week treatment cycle was well tolerated with the majority being mild to moderate gastrointestinal and haematological side effects. In addition, a number of anaemia cases were observed, however these were judged as being primarily related to the underlying disease. Pharmacokinetic data indicate good bioavailability of this HDAC inhibitor and plasma exposure levels yielded significant pharmacodynamic activity as exemplified by time dependent HDAC enzyme inhibition after dosing.

In this first patient cohort, the average treatment duration with resminostat reached approximately nine weeks. Anti-tumour activity of the drug was assessed every six weeks by combination of computer tomography (CT) and positron-emission tomography (PET), a technique which allows the simultaneous evaluation of changes in the metabolic activity and the size of a tumour lesion. Based on established PET/CT evaluation criteria, 10 patients out of 18 benefited from treatment with resminostat with two patients being assessed as partial responders (PR) (i.e. more than 50% reduction in size of tumour lesions) and a further eight patients with stabilization of disease (SD). Based on PET analysis almost all of these patients showed a diminished metabolic activity of their lesions with the majority being evaluated as partial metabolic responders (more than 25% decrease in PET activity). These results are based on intermediate analysis of the data and are therefore subject to final review.

According to the statistical design of the SAPHIRE study (Simon two-stage design), a minimum number of five responders were required in this reported 1st Simon stage in order to extend the study to a second enrolment phase of an additional 15 patients (the 2nd Simon stage). After reaching this threshold the study has recently proceeded into the 2nd Simon stage recruitment phase. Due to the good tolerability and side effect profile observed in this relatively young HL patient population an optional increase of the daily dose of resminostat from 600 mg to 800 mg has been implemented.

Prof Walewski of the Marie-Sk?odowska-Curie Memorial Institute in Warsaw, Poland, the lead investigator of the SAPHIRE study, commented: "Despite the fact that patients with Hodgkin Lymphoma often respond well to first-line treatment with chemotherapy, there is an urgent medical need for new therapeutic approaches for patients relapsing or becoming refractory to standard therapy. For patients not responding to second line high-dose chemotherapy the 5-year progression-free survival rate is as low as 17%. Hodgkin Lymphoma patients are often very young and the repeated use of chemotherapy can lead to secondary tumour developments in addition to the primary lymphatic cancer. Based on the initial data presented on the 1st Simon stage of the trial, we are hopeful that resminostat may provide a new therapy option to relapsed or refractory HL patients."

Dr Bernd Hentsch, Chief Development Officer at 4SC, commented: "We were very pleased with these initial results and are hopeful of the potential of our oral, pan-HDAC Inhibitor resminostat as a monotherapy treatment for advanced Hodgkin Lymphoma patients. We feel that this indication could provide a clinical proof-of-concept for resminostat, which is currently also being evaluated as a combination treatment in solid tumour indications."

About Resminostat (4SC-201)

Resminostat or 4SC-201 is an oral pan-histone-deacetylase (HDAC) inhibitor. HDAC inhibitors epigenetically modify the chromatin structure of tumour cells to cause their differentiation and programmed cell death (apoptosis) and are therefore considered to offer a mechanism of action that has the particular potential to halt tumour progression and induce tumour regression. Resminostat is currently in a Phase II study as a second line treatment for advanced hepatocellular carcinoma (HCC) and in a Phase II study in Hodgkin's lymphoma. In addition, a further Phase I/II study is planned in colon cancer, investigating resminostat as a second-line treatment option in patients with KRAS tumour mutations in combination with the FOLFIRI regimen. In a previous Phase I study with resminostat in patients with various cancer types, stable disease was achieved in over 50% of the patients, whilst the treatment was well tolerated and showed a positive, differentiating pharmacological profile to other drugs in this class.

About SAPHIRE

The SAPHIRE study is an open-label, single-arm, Simon two-stage design Phase II study where resminostat will be given orally daily for five consecutive days, followed by a nine day treatment free period ("5+9" dosing schedule). In the main phase of the study, patients will receive treatment for six cycles (12 weeks). Disease assessments will be performed after treatment cycles three and six by computed tomography in combination with positron emission tomography (PET/CT), as recommended by the International Working Group (IWG) criteria for the evaluation of HL. Patients showing response or stable disease at the end of the main treatment phase may continue to the follow-up phase and can remain on medication for up to one year. The trial will conclude when the last patient remaining will have completed one year of therapy, develops progressive disease or discontinues treatment for other reasons. The study is expected to enrol 33 patients across 10 sites in Poland, Romania and the Czech Republic.

The primary endpoint of the study is to determine the ORR (objective overall response rate) of resminostat in patients who are refractory to first line treatment or have relapsed after responding to first line therapy. The secondary endpoints include assessment of PFS (progression free survival), TTP (time to progression), DOR (duration of response) and OS (overall survival), as well as the analysis of safety and tolerability of the treatment.

About Hodgkin's Lymphoma

Hodgkin's Lymphoma (HL) - formerly known as Hodgkin's Disease - is a cancer of the lymphatic system, which is part of the immune system. The disease is characterised by the prevalence of the Reed-Sternberg cell. In this disease lymphatic cells grow abnormally and then spread beyond the lymphatic system, which eventually compromises the immune system's ability to fight infection. HL represents one main type of cancer of the lymphatic system. Another type, the class of non-Hodgkin's lymphomas, is, however, far more common. Symptoms of HL include the painless swellings of the lymph nodes, spleen or other tissue, as well as fever, weight loss or night sweats.

Therapy options for HL depend on the stage of the disease and number and regions of lymph nodes affected. The first line treatment of HL after the initial diagnosis consists of chemotherapy and/or radiation, achieving cure rates of up to 80%. Standard of care for patients with refractory or relapsing disease after initial therapy comprises salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation. Disease progression is monitored by computed tomography (CT) in combination with magnetic resonance imaging (MRI) or positron emission tomography (PET). In particular the recent incorporation of functional imaging with PET scanning into disease evaluation has provided significant additional information on the outcome of patients with relapsed HL. For patients exhibiting a complete response after salvage chemotherapy, 5 year progression free survival (PFS) is 79%, but this number drops to 59% for patients only exhibiting partial responses and drops further to 17% for patients resistant to second line therapy regimens. Since there is no standard of care in patients with resistant/refractory HL, there is an especially high need to develop novel therapies for these patients.

Legal Note

This document may contain projections or estimates relating to plans and objectives relating to our future operations, products, or services; future financial results; or assumptions underlying or relating to any such statements; each of which constitutes a forward-looking statement subject to risks and uncertainties, many of which are beyond our control. Actual results could differ materially, depending on a number of factors.

4SC AG

4SC AG (ISIN DE0005753818) is a drug discovery and development company focused on autoimmune and cancer indications. Vidofludimus (4SC-101), a small molecule, is currently in a Phase IIb study in rheumatoid arthritis and a Phase IIa exploratory study in inflammatory bowel disease. The company's lead oncology compound, resminostat (4SC-201), a pan histone deacetylase (HDAC) inhibitor, is in Phase II trials in hepatocellular carcinoma and Hodgkin's lymphoma. Two further oncology compounds, 4SC-203 and 4SC-205 are in Phase I studies. 4SC develops drug candidates until proof-of-concept in order to generate value creating partnerships with the pharmaceutical industry in return for advance and milestone payments as well as royalties.

Founded in 1997, 4SC has 94 employees and has been listed on the Prime Standard of the Frankfurt Stock Exchange since December 2005.

For further information, please visit www.4sc.com.

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