Belinostat abstract for European Society for Medical Oncology (ESMO) 2012

9/17/2012 3:22 AM EST

Topotarget
Company Announcement

Belinostat abstract for European Society for Medical Oncology (ESMO) 2012

To NASDAQ OMX Copenhagen A/S
Announcement No. 15-12 / Copenhagen, September 17, 2012

Copenhagen, Denmark – September 17, 2012 – Today Topotarget A/S (NASDAQ OMX:
TOPO) announced that clinical data on belinostat will be made public at the
2012 ESMO Congress’ homepage, www.esmo.org, today September 17, 2012. 

Shown below is the poster abstract with results from the phase I/II clinical
trial of belinostat (PXD101) in combination with idarubicin in patients with
acute myeloid leukemia (AML) (PXD101-CLN-15) that will be made public today on
the ESMO Congress’ homepage. The poster focuses on investigations made to
identify which patient subgroups that could potentially benefit from belinostat
treatment. 

  -- Favorable impact on mainly intermediate cytogenetic risk AML can be
     predicted by gene expression profiling - Results of a phase I/II trial of
     belinostat in combination with idarubicin in AML.

Belinostat (Bel), a histone deacetylase inhibitor (HDACi), has demonstrated
effective cell killing in leukemic cells and shows a synergistic effect in
combination with anthracyclines in vitro. A favorable impact on the dismal
clinical course of acute myeloid leukemia (AML) was suggested (Schlenk et al.
ASH 2008). Recently, the phase I/II trial assessing the efficacy and safety of
two schedules of Bel in patients unfit for intensive induction therapy
confirmed anti-leukemic effect both of Bel alone and in combination with
idarubicin (ClinicalTrials.gov ID: NCT00878722). 

Among the results, we evaluated the role of cytogenetic aberrations on response
to Bel therapy in 41 patients (pts.), of whom cases with intermediate risk
cytogenetics in trend responded better to Bel than patients with high risk
cytogenetics (p=0.14). In the dose-escalation trial, five complete remissions
(CR) and two partial remissions (PR) were observed in 25 AML pts. (28%) with
low/intermediate risk cytogenetic aberrations, whereas no CR and two PR were
seen in 16 high-risk AML pts. (13%). 

Gene expression profiling based on 13 pts. (four CR+PR and nine PD) revealed a
strong gene expression pattern associated with the response to Bel. MLL, a gene
well-known to be involved in epigenetic deregulation, was among the top 20
strongest correlations. Furthermore, differential expression of TP53 was also
of special interest as histone deacetylases have been shown to modulate p53
transcriptional activity. In accordance, gene ontology class comparison
analysis showed a significant enrichment of categories associated with
epigenetic regulation such as “histone methyltransferase activity” and “histone
deacetylase activity”. In addition, the respective gene expression pattern
harbored predictive information as based on an in vitro cell line derived
predictor a blinded Bel response prediction was feasible. 

A trend indicating the potential association of Bel response and intermediate
risk cytogenetics AML has been found. High-risk AML cases might also benefit
from an epigenetic treatment approach with an HDACi. Further randomized studies
are warranted to explore the benefit of Bel in pts. with AML. 

Axel Mescheder, Chief Medical & Development Officer, says, “This phase I/II
trial investigates the explored efficacy of belinostat in combination with dose
escalation idarubicin in patients with AML. Belinostat was administered either
as the standard regimen (30-min IV infusion 1000 mg/m2 belinostat days 1-5
every 3 weeks) or continuous IV infusion (CIV) of 25-1000 mg/m2/day belinostat
day 1-2 every 2 weeks. The study showed anti-leukemic activity in the standard
regimen (objective response rate 17%) as well as in CIV regimens (objective
response rate 31%). The results presented at ESMO indicate that patients with
AML that could potentially benefit from belinostat treatment may be identified
using gene expression profiling and karyotyping. This is important knowledge
for the future clinical development of belinostat”. 



Topotarget A/S

For further information, please contact:

Anders Vadsholt, CEO - Direct: +45 39 17 83 45; Cell: +45 28 98 90 55

Axel Mescheder, CMDO – Direct: +45 39 17 83 14; Cell: +45 51 55 71 66



Background information

About Topotarget
Topotarget (NASDAQ-OMX: TOPO) is an international biopharmaceutical company
headquartered in Copenhagen, Denmark, dedicated to clinical development and
registration of oncology products. Topotarget focuses, in collaboration with
Spectrum Pharmaceuticals, Inc., on the development in pivotal studies of its
lead drug candidate, belinostat, which has shown positive results as a
monotherapy treating hematological malignancies and positive results in solid
tumors. Belinostat may be used in combination with full doses of chemotherapy,
and is in a pivotal trial within PTCL (peripheral T-cell lymphoma). For more
information, please refer to www.topotarget.com. 

Topotarget A/S Safe Harbor Statement
This announcement may contain forward-looking statements, including statements
about our expectations of the progression of our preclinical and clinical
pipeline including the timing for commencement and completion of clinical
trials and with respect to cash burn guidance. Such statements are based on
management's current expectations and are subject to a number of risks and
uncertainties that could cause actual results to differ materially from those
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that there can be no assurance that actual results or business conditions will
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statements as a result of various factors, including, but not limited to, the
following: The risk that any one or more of the drug development programs of
Topotarget A/S will not proceed as planned for technical, scientific or
commercial reasons or due to patient enrolment issues or based on new
information from non-clinical or clinical studies or from other sources; the
success of competing products and technologies; technological uncertainty and
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history of incurring losses and the uncertainty of achieving profitability;
Topotarget A/S' stage of development as a biopharmaceutical company; government
regulation; patent infringement claims against Topotarget A/S' products,
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proprietary rights; uncertainties relating to commercialization rights; and
product liability exposure. We disclaim any intention or obligation to update
or revise any forward-looking statements, whether as a result of new
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