BELINOSTAT DATA PRESENTATION AT 101ST ANNUAL MEETING OF THE AMERICAN ASSOCIATION FOR CANCER RESEARCH

Topotarget A/S
Symbion
Fruebjergvej 3
DK 2100 Copenhagen
Denmark
Tel: +45 39 17 83 92
Fax: +45 39 17 94 92
CVR-nr: 25695771
www.topotarget.com




Copenhagen, Denmark - 21 April, 2010 - Topotarget A/S (NASDAQ OMX: TOPO.CO) US
partner, Spectrum Pharmaceuticals, Inc. (NASDAQGM: SPPI) announces belinostat
pre-clinical data presented at 101ST annual meeting of the American association
for cancer research 

•	Data Suggest HDAC Inhibitors, Such as Belinostat, May Be Efficacious in the
Treatment of Small Cell Lung Cancer 
•	Results Indicate Synergy With Conventional Chemotherapy Agents

Spectrum Pharmaceuticals, Inc. (NasdaqGM: SPPI), a commercial-stage
biotechnology company with a primary focus in oncology, today announced results
of a pre-clinical study conducted by the National Cancer Institute of
belinostat in the treatment of small-cell lung cancer that was presented in a
poster session on Wednesday, April 21, 2010 at the 101st Annual Meeting of the
American Association for Cancer Research (AACR), being held at the Walter E.
Washington Convention Center in Washington, DC. 

“Based on the data presented today at AACR, we believe belinostat may be an
effective treatment option for small-cell lung cancer,” said Rajesh C.
Shrotriya, MD, Chairman, President and Chief Executive Officer of Spectrum
Pharmaceuticals, Inc.  “While we continue to enroll patients into the
100-evaluable patient registrational trial for belinostat in peripheral T-cell
lymphoma (PTCL), being conducted under a Special Protocol Assessment by the
FDA, we are exploring potential clinical trial design options for the treatment
of lung cancer.” 

Abstract #5372 - Synergy of Histone Deacetylase Inhibitors, Belinostat and
Depsipeptide, With DNA Damaging Agents, Etoposide and Cisplatin, In Small Cell
Lung Cancer Cell Lines 
Small Cell Lung Cancer (SCLC) is the most aggressive type of lung carcinoma. 
SCLC has a high response rate to chemotherapy, but rapid onset of drug
resistance.  Chemotherapeutic treatment using combinations of drugs that target
different signaling pathways have demonstrated improvement in overall survival
of patients with SCLC.  HDAC inhibitors play a role in regulating cell cycle
progression and have been suggested as potential therapeutic agents for SCLC. 
HDAC inhibition is believed to relax DNA, thereby allowing increased access of
transcription factors to certain promoters.  Likewise, these agents could
increase accessibility of DNA to cytotoxic agents. 

Two distinct HDAC inhibitors, belinostat and depsipeptide, were examined to
determine whether they have an effect on SCLC lines and whether they could be
combined with conventional chemotherapy agents etoposide and cisplatin for
SCLC. 

Simultaneous and schedule-depended treatment protocols of SCLC cells with
single drugs and drug combinations were used.  Computational analysis of cell
survival using combination index (CI) showed that HDAC inhibitors synergized
with DNA damaging agents when administered simultaneously, but this effect was
only additive if cells were pre-treated with HDAC inhibitors for 24 hours prior
to DNA damaging agents.  In addition, using DNA damaging agents 24 hours prior
to HDAC inhibitors was clearly antagonistic with CI>1 for all drugs and cell
lines tested. 

Because of a potential use of belinostat and depsipeptide for therapy of SCLC
in combination with conventional chemotherapies, the mechanisms of synergy and
protection between these agents were examined. PolyADP-ribose polymerase (PARP)
degradation was complete when drugs were used simultaneously, but was decreased
if HDAC inhibitors were used prior to cisplatin or etoposide. The degradation
of PARP enzyme prevents repair of DNA strand breaks caused by chemotherapeutic
agents and thereby facilitates the programmed cell death, or apoptosis, of
cancer cells. Therefore, a greater degree of PARP degradation is indicative of
a greater capacity of a given anti-cancer agent or a combination of agents to
induce apoptosis. 

It was concluded that HDAC inhibitors synergize with DNA damaging agents only
if administered simultaneously. Treatment of cells with HDAC inhibitors and DNA
damaging agents induces PARP degradation. Combination of HDAC inhibitors with
etoposide does not affect single stranded DNA damage. Simultaneous treatment
with DNA damaging agents increases double strand DNA damage. The design of
clinical trials for combination of HDAC inhibitors and chemotherapeutic agents
should take into account the timing that induces maximum effect. 


TopoTarget A/S

For further information, please contact:

Francois Martelet, CEO: Direct: +45 39 17 94 99; Mobile: +45 31 36 83 41
Anders Vadsholt, CFO: Direct: +45 39 17 83 45; Mobile: +45 28 98 90 55


Background information

About TopoTarget

TopoTarget (NASDAQ OMX: TOPO) is an international biotech company headquartered
in Denmark, dedicated to finding ''Answers for Cancer'' and developing improved
cancer therapies. TopoTarget currently focuses, in collaboration with Spectrum
Pharmaceuticals, Inc., on the development in pivotal studies of its lead drug
candidate, belinostat, which has shown proof-of-concept as monotherapy in
treating haematological malignancies and positive results in solid tumours.
Belinostat can be used in combination with full doses of chemotherapy, and is
currently in a pivotal trial within PTCL (peripheral T-cell lymphoma).
TopoTarget's key cancer drugs target HDAC, NAD+, mTOR, Fas ligand and
topoisomerase II. The company's first marketed product, Savene®/Totect®, was
approved by EMEA in 2006 and the FDA in 2007, and is marketed by TopoTarget's
own sales force in the US. For more information, please refer to
www.topotarget.com. 


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