Belinostat acts synergistically when combined with castration and anti-hormone therapy. Pre-clinical data presented in Barcelona

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 - November 28, 2009 - TopoTarget A/S (OMX: TOPO) announced
today that data from a pre-clinical study in aggressive hormone refractory
prostate cancer cell lines and in xenografts demonstrate that prostate cancer
cell lines are all sensitive to belinostat inhibition and that belinostat can
increase the sensitivity towards anti-hormone therapy and as a result become
attractive in the treatment of hormone refractory prostate cancers. Data were
presented by Claudio Festuccia et al from the University of L'Aquila, Italy at
the 2nd Multidisciplinary Meeting on Urological cancers in Barcelona EMUC-ESMO. 

Background:
Prostate cancer is the most frequently diagnosed malignancy and one of the
leading causes of cancer death in men accounting for about 10% of male cancers
of North America and Western\ Northern Europe. Although androgen ablation
therapy (castration) induces remission in 80-90% of men with advanced prostate
cancer, the majority of prostate cancer patients develop treatment resistance
with a median time of 18-24 months to disease progression. One hypothesis is
that some of the mechanisms that are normally under androgen control become
constitutively active in androgen-independent tumor cells. Histone
modifications acetylation and deacetylation are the major driving force for
epigenetic gene regulation. It has been established that Histone deacetylases
(HDAC) are up-regulated in most human cancers. HDAC inhibitors (HDACIs) are a
novel class of relatively specific anticancer drugs, which were originally
identified by their capacity to reverse the transformed phenotype. 

Conclusion:
Taken together, the results demonstrate a clear antineoplastic effect of
belinostat against the prostate cancer cell lines and that sensitization to the
antihormone agent Biclutamide pointed towards that the combined therapy based
on Belinostat and Bicalutamide may offer a new pharmacological tool in the
treatment of castration resistant prostate cancer. 

TopoTarget A/S


For further information, please contact:

Peter Buhl Jensen	Telephone	+45 39 17 94 99
CEO		Mobile	+45 21 60 89 22
Background information

About belinostat
Belinostat is a promising small molecule HDAC inhibitor being investigated for
its role in the treatment of a wide range of solid tumors and hematologic
malignancies either as a single-agent, or in combination with other active
anti-cancer agents, including carboplatin, paclitaxel, cis-retinoic acid,
azacytidine and Velcade® (bortezomib) for injection. HDAC inhibitors represent
a new mechanistic class of anti-cancer therapeutics that target HDAC enzymes,
and have been shown to: arrest growth of cancer cells (including drug resistant
subtypes); induce apoptosis, or programmed cell death; promote differentiation;
inhibit angiogenesis; and sensitize cancer cells to overcome drug resistance
when used in combination with other anti-cancer agents. 
Intravenous belinostat is in phase III in peripheral T-cell lymphoma (PTCL) and
is currently being evaluated in multiple clinical trials as a potential
treatment for, cancer of unknown primary (CUP), ovarian cancer, small cell lung
cancer, thymoma, liver, soft tissue sarcoma, lymphoma, AML, Myelodysplastic
Syndrome (MDS),  either alone or in combination with other anti-cancer
therapies. Continuous intravenous administration (CIV) is being evaluated in
clinical trials in solid tumours as well as in AML.  An oral formulation of
belinostat is also being evaluated in a Phase I clinical trial for patients
with advanced solid tumors. Several trials in the belinostat program are
conducted under a Clinical Trials Agreement (CTA) under which the NCI sponsors
clinical trials to investigate belinostat for the treatment of various cancers,
both as a single-agent and in combination chemotherapy regimens. Furthermore
TopoTarget has a Cooperative Research and Development Agreement (CRADA) with
the NCI to conduct preclinical and nonclinical studies on belinostat in order
to better understand its anti-tumor activity and to provide supporting
information for clinical trials. 

About TopoTarget 
TopoTarget (OMX: TOPO) is an international biotech company headquartered in
Denmark, dedicated to finding ''Answers for Cancer'' and developing improved
cancer therapies. The company was founded and is run by clinical cancer
specialists and combines years of hands-on clinical experience with in-depth
understanding of the molecular mechanisms of cancer. 
TopoTarget has a broad clinical pipeline but is currently focusing on the
development of belinostat, which has shown proof of concept as monotherapy in
treating haematological malignancies and positive results in solid tumours
where it can be used in combination with full doses of chemotherapy, and is in
phase III in PTCL. TopoTarget's expertise in translational research is
utilizing its highly predictive in vivo and in vitro cancer models. TopoTarget
is directing its efforts on key cancer targets including HDACi, NAD+, mTOR,
FasLigand and topoisomerase II inhibitors. 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 Europe and the US. For more
information, please refer to www.topotarget.com.