DGAP-News: Press Release: 4SC gives update on the clinical development of its lead cancer compound resminostat
(firmenpresse) - DGAP-News: 4SC AG / Key word(s): Miscellaneous
Press Release: 4SC gives update on the clinical development of its
lead cancer compound resminostat
30.05.2013 / 07:30
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Press Release
4SC gives update on the clinical development of its lead cancer compound
resminostat
- Data from completed Phase I part of SHORE study in advanced colorectal
cancer (CRC) to be presented at upcoming ASCO conference in Chicago,
confirming the safety of the resminostat FOLFIRI combination and
showing encouraging signs of clinical benefit
- Successful identification of a biomarker (ZFP64) indicative of survival
in both advanced liver cancer (HCC) and Hodgkin's Lymphoma (HL) Phase
II clinical trials with resminostat
- Main focus of the further clinical development of resminostat to be on
pivotal programme in first-line advanced HCC with an intended
integrated biomarker program including ZFP64
Planegg-Martinsried, Germany, 30 May 2013 - 4SC AG (Frankfurt, Prime
Standard: VSC), a discovery and development company of targeted small
molecule drugs for autoimmune diseases and cancer, today announced an
update on substantial progress in the clinical development of its lead
oncology drug resminostat.
Results from the completed Phase I part of the SHORE study in advanced CRC
Positive Phase I results on safety, tolerability and pharmacokinetics from
its SHORE study with resminostat in combination with FOLFIRI chemotherapy
in patients with advanced colorectal cancer (CRC) will be presented at the
upcoming 2013 meeting of the American Society of Clinical Oncology (ASCO)
in Chicago on 2 June 2013. The SHORE study has been designed to investigate
the combination of resminostat and FOLFIRI as a new second-line treatment
option for patients with advanced, KRAS-mutant CRC.
Resminostat proved to be safe and well-tolerated in all doses tested,
applying its standard 5+9 dosing regimen up to a daily dosage of 600 mg
(once daily (OD)) or 800 mg (400 mg twice daily (BID)) in combination with
the recommended standard dosage of FOLFIRI, a multi-component chemotherapy
regimen that includes e.g. 5-fluorouracil (5-FU) and irinotecan. This again
confirmed the clean safety profile of resminostat when applied in
combination with established cancer therapies. Observed side effects were
generally mild to moderate and occurred, as expected, primarily as
gastrointestinal and hematological effects. No dose-limiting toxicities
(DLT) occurred and no formal maximum tolerated dose (MTD) of the
combination regimen was determined up to the highest dose level of 800 mg
(400 mg BID) resminostat. The known side-effect profile of the FOLFIRI
regimen did not change as a result of the additional administration of
resminostat. The study further confirmed the favorable pharmacokinetic
profile of resminostat already observed in other studies, reflected for
instance in the dose proportionality of resminostat blood levels. No
pharmacological interactions between resminostat and any of the FOLFIRI
components were observed.
In addition, the treatment - already in the Phase I part of the study -
showed encouraging signs of clinical activity. Patients frequently
experienced disease stabilisation as clinical benefit and, accordingly,
could be treated with the combination of resminostat and FOLFIRI for
several months: 7 of 15 evaluable patients were treated for at least 12
weeks with a maximum of 33 weeks.
Enno Spillner, Chief Executive Officer of 4SC AG, comments: 'We have
successfully achieved the study objective of the Phase I part of our SHORE
trial. The data have once again confirmed the clean safety profile of
resminostat when applied in combination with established cancer therapies.
In addition, the resminostat FOLFIRI combination therapy has shown
encouraging signs of clinical benefit in colorectal cancer (CRC). After
having shown convincing Phase II data in our main indication liver cancer
(HCC) last year, these new Phase I results in CRC once again illustrate the
great clinical potential of our key compound resminostat.'
The ASCO poster will be available at
http://www.4sc.de/product-pipeline/publications-posters/resminostat when
the presentation begins at 8:00 am CDT (3:00 pm CEST) on 2 June 2012.
As previously communicated, 4SC will primarily focus on the further
development of resminostat toward market approval as a first-line drug for
treatment of advanced liver cancer (HCC). 4SC is currently working on the
clinical development plan for resminostat, used in combination with
sorafenib as a first-line therapy of HCC, and will then discuss the further
development steps with potential partners and regulatory authorities in the
EU and the US.
Identification of ZFP64 gene expression as a biomarker indicative of
survival in clinical trials with resminostat in both liver cancer (HCC) and
Hodgkin lymphoma (HL)
4SC also reports promising biomarker data from two Phase II clinical trials
with resminostat in advanced liver cancer (hepatocellular carcinoma, HCC)
(SHELTER study) and advanced Hodgkin lymphoma (HL) (SAPHIRE study). These
observations in both HCC and HL patients point to a role of the gene
expression levels of a certain gene, called Zinc Finger Protein 64 (ZFP64),
as a potential biomarker suitable to indicate the clinical outcome of
cancer diseases when treated with resminostat.
A promising positive correlation between expression levels of ZFP64 in
peripheral blood cells of HCC and HL patients at baseline, i.e. before the
start of resminostat treatment, and the achieved clinical outcome, was
observed. High baseline ZFP64 expression levels were linked to an increased
clinical benefit, i.e. patients were more likely to achieve clinical stable
disease (SD). More importantly, patients displaying higher ZFP64 baseline
levels also experienced a significantly longer overall survival (OS)
compared to patients with lower ZFP64 baseline levels.
These findings were observed in patient cohorts from Phase II studies with
resminostat in two different advanced cancer indications, liver cancer
(hepatocellular carcinoma, HCC) and Hodgkin's Lymphoma (HL). This may
suggest a common underlying biological cancer cell background in both
tumors types, which might be more responsive to treatment with resminostat.
A patent application has been filed in order to provide adequate IP
protection for these findings. ZFP64 has been described in the scientific
literature as a transcription factor and co-activator of Notch, a protein
controlling one of the central signaling pathways involved in the
regulation of cancer.
Data were derived from the analysis of changes in gene expression patterns
in response to both resminostat monotherapy (SAPHIRE study in HL and
SHELTER study in HCC) and in combination with sorafenib (Nexavar(R))
(SHELTER study in HCC). The initial goal of the biomarker analysis was to
investigate whether changes in expression levels of these genes in
peripheral blood cells may serve as further pharmacodynamic markers for the
pharmacological activity of resminostat.
Dr Bernd Hentsch, Chief Development Officer of 4SC AG; comments: '4SC will
now conduct further studies to confirm these positive findings. It is our
goal to develop resminostat, ideally in conjunction with the use of
biomarkers as a personalized cancer medicine, towards market approval. As a
part of this strategy, 4SC will integrate these new findings about ZFP64 ina biomarker program for the further development of resminostat in
first-line HCC. Therefore, going forward, 4SC will discuss the resulting
options with potential partners and regulatory authorities.'
Ends
Details of the Presentation:
Abstract No.: 3625
Abstract Title: Phase I dose escalation of the oral histone deacetylase
inhibitor (HDACi) resminostat in combination with FOLFIRI in colorectal
cancer (CRC) patients: the SHORE trial
Time/Place of Presentation: Sunday, 2 June 2013, 8:00 am - 11:45 am, S Hall
A2
Poster Session: General Poster Session, Gastrointestinal (Colorectal)
Cancer
Authors: H. Schulze-Bergkamen1, D. Jäger1, HG Kopp2, M. Bitzer2, A. Mais3,
K. Resemann3, B. Hauns3, J. Asche3, S.W. Henning3, B. Hentsch3
(1National Center for Tumor Diseases (NCT) Heidelberg, Germany, 2University
of Tuebingen Medical Center, Tuebingen, Germany, 34SC AG,
Planegg-Martinsried, Germany)
About Resminostat
Resminostat (4SC-201), 4SC's lead oncology compound, is an oral
pan-histone-deacetylase (HDAC) inhibitor with an innovative epigenetic
mechanism of action that potentially enables the compound to be deployed as
a novel, targeted tumour therapy for a broad spectrum of oncological
indications, both as a monotherapy and, in particular, in combination with
other cancer drugs. HDAC inhibitors have been shown to modify the DNA
structure of tumour cells and 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. Additionally, resminostat is also assumed to
induce what is known as tumour cell (re-)sensitisation to other anti-cancer
compounds. This process can suppress or reverse certain tolerance and
resistance mechanisms which tumour cells often develop against other cancer
drugs. Supplementary treatment with resminostat can be expected to restore
or significantly improve the efficacy of a previously administered cancer
therapy that was no longer effective; furthermore, combining resminostat
and common cancer drugs right from the very beginning can also be expected
to effectively enhance the success of such a treatment.
Resminostat has been introduced into a Phase II programme in the three
indications of liver cancer (hepatocellular carcinoma, HCC), Hodgkin
Lymphoma (HL), and colorectal cancer (CRC). In the Phase II SAPHIRE trial
in patients with advanced HL, resminostat in monotherapy has demonstrated
substantial anti-tumour activity, with an overall response rate of 34% and
a clinical benefit in 54% of the patients in a heavily pre-treated patient
population together with very good safety and tolerability. In the Phase
I/II SHORE study, which evaluates resminostat in combination with the
chemotherapeutic FOLFIRI regimen as a second-line treatment of KRAS-mutant
CRC patients, positive results for safety and tolerability of this
combination will be published at this year's ASCO conference in Chicago.
Furthermore, in the Phase II SHELTER study resminostat has been evaluated
as monotherapy and in combination with sorafenib as a second-line treatment
in advanced HCC after proven radiological disease progression under
first-line sorafenib therapy. Patients receiving the resminostat/sorafenib
combination therapy had shown a progression-free survival rate (PFSR) after
12 weeks of 70.0% and a median PFS of 4.7 months, resulting in a median
overall survival (OS) of 8.0 months.
4SC is currently in discussions with regulatory agencies and potential
partners in order to prepare the next advanced clinical development steps
for resminostat in combination with sorafenib as a first-line treatment for
patients with advanced HCC.
About 4SC
The Group managed by 4SC AG (ISIN DE0005753818) discovers and develops
targeted, small-molecule drugs for treating diseases with high unmet
medical needs in cancer and autoimmune indications. These drugs are
intended to provide innovative treatment options that are more tolerable
and efficacious than existing therapies, and provide a better quality of
life. The Company's pipeline comprises promising products that are in
various stages of clinical development. 4SC's aim is to generate future
growth and enhance its enterprise value by entering into partnerships with
pharmaceutical and biotech companies. Founded in 1997, 4SC had 86 employees
at 31 March 2013. 4SC AG has been listed on the Prime Standard of the
Frankfurt Stock Exchange since December 2005.
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.
For more information please visit www.4sc.com or contact:
4SC AG
Jochen Orlowski, Corporate Communications&Investor Relations
jochen.orlowski(at)4sc.com, Tel.: +49-89-700763-66
MC Services
Raimund Gabriel, Mareike Mohr
raimund.gabriel(at)mc-services.eu , Tel.: +49-89-210228-30
mareike.mohr(at)mc-services.eu, Tel.: +49-89-210228-40
The Trout Group (USA)
Chad Rubin
Crubin(at)troutgroup.com, Tel.: +1-646-378-2947
End of Corporate News
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Language: English
Company: 4SC AG
Am Klopferspitz 19a
82152 Martinsried
Germany
Phone: +49 (0)89 7007 63-0
Fax: +49 (0)89 7007 63-29
E-mail: public(at)4sc.com
Internet: www.4sc.de
ISIN: DE0005753818
WKN: 575381
Listed: Regulierter Markt in Frankfurt (Prime Standard);
Freiverkehr in Berlin, Düsseldorf, München, Stuttgart
End of News DGAP News-Service
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