Copenhagen, Denmark – February 29, 2012 – Today Topotarget A/S (NASDAQ OMX:
TOPO) announced that clinical data on belinostat will be presented at the 2012
American Association for Cancer Research Annual Meeting (AACR), March 31 –
April 4, 2012.


Shown below is the abstract that is now available for viewing on the AACR
website (http://www.aacr.org/).


Abstract 759, Sunday, April 1, 2012 at 1.00-5.00 pm, McCormick Place West (Hall
F).


Quantitation of the HDAC inhibitor belinostat (PXD-101) and metabolites in
human plasma by a novel LC-MS/MS assay.

Brian F. Kiesel, Robert A. Parise, Jette Tjørnelund, Mette K. Christensen,
Einars Loza, Edward Chu, Shivaani Kummar, Jan H. Beumer


Background:
Histone deacetylases (HDAC) are frequently deregulated in human cancers and
their inhibition allows re-expression of silenced genes. Belinostat is an HDAC
inhibitor with in vitro and in vivo activity in multiple malignancies,
currently in phase II trials. To date, the pharmacokinetics and metabolism of
belinostat have not been adequately characterized. To support an organ
dysfunction study and clinical development of belinostat, we developed and
validated an LC-MS/MS assay for the sensitive, accurate, and precise
quantitation of belinostat and its metabolites belinostat-glucuronide,
methylated-belinostat, belinostat amide, 3-ASBA, and belinostat acid in human
plasma.

Methods:
The assay used 50 µL of plasma, [13C6]-belinostat and [D5]-3-ASBA as internal
standards and acetonitrile (0.1% TFA) for protein precipitation. A UPLC C18
column was used with a gradient elution from 90:10 to 10:90 water-acetonitrile
(0.1% formic acid) over the course of 4 min followed by re-equilibration for 3
min (7 min total run time). Flow rate was 0.5 mL/min. An ABI 4000 tandem MS/MS
with ESI positive and negative ionization in MRM mode was used to detect the
analytes. Bioanalytical method validation was performed based on FDA
guidelines. The applicability of the assay was demonstrated by quantitating
belinostat and its metabolites in plasma of a human patient sampled over the
course of 24 h.

Results:
Belinostat eluted at 2.9 min, while all metabolites eluted between 2.7 and 3.6
min. The assay was linear and accurate between 30 and 5000 ng/mL for all
analytes; 3 triplicate standard curves assayed on 3 separate days displayed a
CV <19% at each of 6 different calibration points (30, 100, 300, 1000, 3000,
5000 ng/mL) for belinostat and CV <29% for the metabolites. The accuracy of the
assay was between 101% and 106% at 4 different QC levels (30, 100, 2500, and
4000 ng/mL) for belinostat and between 96% and 117% for metabolites, while the
precision was <17% at each concentration for belinostat and <26% for
metabolites. Recovery was >69% for belinostat and >64% for metabolites.
Belinostat and all metabolites could be quantitated in human plasma after IV
administration of belinostat over 30 min. Belinostat glucuronide appeared to be
the major metabolite with up to 10-fold exposure relative to belinostat.

Conclusion:
We have developed a sensitive, accurate, and precise LC-MS/MS assay that allows
quantitation of belinostat and its 5 metabolites in human plasma. UGT1A1 is
responsible for glucuronidation, which appears to be a major metabolic route.
This assay will be a valuable tool to assess the pharmacokinetics and
metabolism of belinostat in humans, and it is being used to support clinical
studies employing belinostat in multiple clinical trials.


Topotarget A/S

For further information, please contact:

Francois Martelet, CEO: Direct: +45 39 17 83 43; Mobile: +45 51 32 83 41

Anders Vadsholt, CFO: Direct: +45 39 17 83 45; Mobile: +45 28 98 90 55


Background information

About Topotarget A/S
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
described in the forward-looking statements. Topotarget A/S cautions investors
that there can be no assurance that actual results or business conditions will
not differ materially from those projected or suggested in such forward-looking
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
product development risks; uncertainty of additional funding; Topotarget A/S'
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,
processes and technologies; the ability to protect Topotarget A/S' patents and
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
information, future events, or otherwise, unless required by law.

Announcement no. 03-12 Abstract for American Association for Cancer Research 2012.pdf