DGAP-News: 4SC Announces Treatment of First Patient in Phase I TOPAS Study with the selective HDAC inhibitor 4SC-202
(firmenpresse) - DGAP-News: 4SC AG / Key word(s): Miscellaneous
4SC Announces Treatment of First Patient in Phase I TOPAS Study with
the selective HDAC inhibitor 4SC-202
13.04.2011 / 07:30
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Planegg-Martinsried, Germany, 13 April, 2011 - 4SC (Frankfurt, Prime
Standard: VSC), a drug discovery and development company, today announced
that the first patient has been treated in the Phase I TOPAS study with
4SC-202, a selective histone deacetylase (HDAC) inhibitor which is also
characterized by an anti-mitotic mechanism of action. The study will
evaluate the safety, pharmacokinetics and clinical efficacy of orally
administered 4SC-202 in patients with advanced hematological indications,
including acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL),
chronic lymphocytic leukemia (CLL), multiple myeloma (MM), myelodysplastic
syndrome (MDS) and lymphomas. This is the second HDAC-inhibitor in 4SC's
oncology portfolio, in addition to resminostat, a pan-HDAC inhibitor.
TOPAS is a mono-centric, single arm, open-label dose escalation Phase I
study designed to evaluate daily doses between 25 and 400mg of 4SC-202 in
six dose cohorts. Patients will be given 4SC-202 tablets once daily for 14
consecutive days (d1-14) in a 21-day treatment cycle (14+7 scheme). The
main study phase will consist of two treatment cycles and patients
benefiting from treatment at the end of the main study phase may remain on
therapy in a subsequent follow-up phase. Stepwise escalation of the initial
starting dose (25mg) will occur according to a standard 3+3 design. Each
dose cohort will include up to 6 patients and the study is currently
planned to enroll up to 36 patients in total. Depending on the observed
pharmacokinetic profile and the tolerability of once daily doses of
4SC-202, alternative dosing schedules such as twice daily administration
will also be evaluated.
The primary objective of the TOPAS study is to investigate the safety,
tolerability and pharmacokinetics of 4SC-202 and the associated
determination of optimal doses and dosing regimens for patients with
advanced hematological malignancies. Secondary objectives include the
assessment of the clinical anti-tumour activity with respect to tumour
response, duration of response (DOR) and progression-free survival (PFS) of
the patients. Additional exploratory objectives include the evaluation of
relevant biomarkers such as histone deacetylase (HDAC) enzymatic inhibition
and induction of increased histone acetylation by 4SC-202 in peripheral
mononuclear cells (PBMC) of patients as well as the analysis of altered
gene expression profiles in patient blood. The study will be performed in
one centre in Germany and is expected to report results in 2012.
Inhibition of histone deacetylases (HDAC) is believed to offer a promising
therapeutic option in oncology drug development. Selected hematological
malignancies which were described to be particularly sensitive to HDAC
inhibition, are currently targeted by two marketed compounds of this class
which have been approved for cutaneous T-cell lymphoma (CTCL).
In contrast to 4SC's pan-HDAC inhibitor resminostat, 4SC-202 represents a
selective inhibitor of class I HDAC enzymes and has shown potent
anti-tumour activity in a variety of in vitro and in vivo preclinical
models associated with good pharmacokinetic characteristics and good
overall tolerability. The compound has also demonstrated a particularly
effective anti-mitotic effect, which inhibits the process of cell division
and introduces tumour cell death (apoptosis).
'With the commencement of the TOPAS study we have now advanced the second
HDAC inhibitor to the clinical development stage and extended our oncology
pipeline to a total of four compounds. Due to its selective inhibition
profile on class I HDACs, as well as its pronounced pharmacological effect
on the cell cycle, we anticipate to see a significant clinical efficacy of
4SC-202 in patients with advanced hematological malignancies combined with
an acceptable side effect profile,' commented Dr. Bernd Hentsch, Chief
Development Officer at 4SC.
More information about this study can be found on www.clinicaltrials.gov
-End-
About 4SC-202
4SC-202 is a benzamide type selective inhibitor of human class I HDAC
isoenzymes 1, 2 and 3. HDAC inhibitors modify the DNA 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.
4SC-202 was extensively studied in preclinical development where it has
shown anti-proliferative activity against a broad spectrum of human tumour
cell lines in vitro as well as in various in vivo tumour models
representing different cancer indications. 4SC-202 additionally provides a
potent anti-mitotic activity by arresting the cell cycle and disrupting the
mitotic spindle apparatus, which are both essential for the orderly
division and proliferation of cells, thereby introducing apoptotic cell
death. This specific pharmacological mode of action might be responsible
for the enhanced anti-proliferative effect of 4SC-202 observed in
preclinical studies which may translate into significant additional
anti-tumour activity in the clinic.
About 4SC
4SC AG (ISIN DE0005753818) discovers and develops targeted small molecules
for autoimmune and cancer indications. Vidofludimus (4SC-101), an IL-17
inhibitor, is currently in Phase II development in rheumatoid arthritis
(RA) and inflammatory bowel disease (IBD), for which positive results from
a Phase IIa study were recently reported. The company's lead oncology
compound, resminostat (4SC-201), an oral pan-histone deacetylase (HDAC)
inhibitor, is in Phase II trials in hepatocellular carcinoma, Hodgkin's
lymphoma and KRAS-mutant colorectal cancer. 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.
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 contact:
4SC AG
Yvonne Alexander
Investor&Public Relations
Tel.: +49 (0) 89 70 07 63 - 0
MC Services (Europe)
Raimund Gabriel
Tel.: +49 (0) 89 21 02 28 - 40
The Trout Group (USA)
Chad Rubin
Tel.: +1 646 378 2947
End of Corporate News
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Language: English
Company: 4SC AG
Am Klopferspitz 19a
82152 Martinsried
Deutschland
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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119515 13.04.2011
Datum: 13.04.2011 - 07:30 Uhr
Sprache: Deutsch
News-ID 33766
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