Initiation of phase 1/2 study of belinostat in combination for thymic malignancies

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 - 19 March, 2010 - TopoTarget A/S (NASDAQ OMX: TOPO) and
Spectrum Pharmaceuticals Inc. (NASDAQ: SPPI) announced today that the first
patient has been dosed in the National Cancer Institute (NCI)-sponsored phase
1/2 trial of belinostat in combination with cisplatin, doxorubicin and
cyclophosphamide in  first line treatment of advanced or recurrent thymic
malignancies. The primary study objective in the phase 1 portion is to
determine the recommended phase 2 dose for the combination of belinostat plus
cisplatin, doxorubicin and cyclophosphamide. The phase 2 portion will measure
clinical response rate. The study is expected to recruit between 30 and 48
patients. 

“We are very happy for the solid work and support the NCI are doing to bring
effective treatment to patients with thymic malignancies - and we are proud
that belinostat has been chosen by the NCI for further development. Provided
that good phase 1/2 data emerge this work may be the basis of building up a
regulatory dossier aiming at gaining a marketing authorization in both the US
and EMEA,” said Francois Martelet, MD, CEO of TopoTarget. 

The study
Phase 1/2 Study of Belinostat (PXD-101) in combination with cisplatin,
doxorubicin and cyclophosphamide in first line treatment of advanced or
recurrent thymic malignancies. 

Primary Objective
In the phase 1 portion, the primary objective will be to determine the safe and
tolerable phase 2 dose, dose limiting toxicities and preliminary activity for
the combination of belinostat by continuous IV infusion (CIV) with cisplatin,
doxorubicin and cyclophosphamide. 
In the phase 2 portion the primary objective will be to determine the clinical
response (PR and CR) of the drug combination. 

Schedule and Dosing
•	Belinostat will be given as a 48h continuous infusion starting on day one,
doxorubicin as slow IV injection on days 2 and 3, cisplatin will be infused
over 1 hour on day 2 and cyclophosphamide as slow infusion on day 3 
•	Treatment will be given every 21 days for no more than six cycles or until
disease progression Treatment with belinostat alone may continue until disease
progression. 


Today's news does not change TopoTarget's full-year financial guidance.



TopoTarget A/S

For further information, please contact:

Francois Martelet	Telephone	+45 39 17 94 99
CEO
	
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, doxorubicin, idarubicin,
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, (programmed cell death);
promote differentiation; inhibit angiogenesis; and sensitize cancer cells to
overcome drug resistance when used in combination with other anti-cancer
agents. Company-sponsored trials of IV-administered belinostat include a
pivotal trial in peripheral T-cell lymphoma (PTCL), a randomized controlled
Phase 2 trial in cancer of unknown primary (CUP), and studies in ovarian,
colorectal and soft tissue sarcoma patients. NCI-sponsored trials (single agent
and in combination with anti-cancer therapeutics) with IV-administered
belinostat include studies in hepatocellular, thymoma, Myelodysplastic Syndrome
(MDS), and other solid and hematologic cancers. 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 1 clinical trial for patients with advanced solid tumors and lymphomas.
NCI-sponsored clinical trials are being conducted under a clinical trials
agreement between NCI and TopoTarget. 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.
The NCI is an agency of the U.S. government that oversees the U.S. National
Cancer Program, conducts cancer research, and provides funding for research and
training.” 

About Thymoma and Tymic carcinoma
The thymus, a small organ that lies in the upper chest under the breastbone, is
part of the lymph system. It makes white blood cells, called lymphocytes, that
protect the body against infections. There are different types of tumors of the
thymus. Thymomas and thymic carcinomas are rare tumors (approximate incidence
of 0.15 cases per 100,000) of the cells that are on the outside surface of the
thymus. The tumor cells in a thymoma look similar to the normal cells of the
thymus, grow slowly, and rarely spread beyond the thymus. On the other hand,
the tumor cells in a thymic carcinoma look very different from the normal cells
of the thymus, grow more quickly, and spread to other parts of the body when
the cancer is found . Thymic carcinoma is more difficult to treat than thymoma.
Chemotherapy is efficacious in the systemic treatment of thymomas and thymic
carcinomas. Single agents have activity in the range of 10-20%, and cisplatin
alone achieves 10% response rate. However combination chemotherapy achieves
higher response rates; the most active combinations include cisplatin, and
response rates are in the range of 40-90%. Common first line combinations
include cisplatin-etoposide, cisplatin-etoposide-ifosfamide, and
cisplatin-doxorubicincyclophosphamide, and several variations. A large
proportion of patients with advanced stages however cannot be cured with
available treatments and at least 50% of these patients require second-line
therapy. Several agents have been shown to have some activity in this setting.
Responses seen in previously cisplatin-treated thymomas are however relatively
short-lived and there is need of novel agents in this disease. 

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
in a pivotal trial within PTCL (peripheral T-cell lymphoma). TopoTarget's
expertise in translational research is based on utilising 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. 


About Spectrum Pharmaceuticals
Spectrum Pharmaceuticals is a commercial-stage biotechnology company with a
focus in oncology. The Company's strategy is comprised of acquiring and
developing a broad and diverse pipeline of late-stage clinical and commercial
products; establishing a commercial organization for its approved drugs;
continuing to build a team with people who have demonstrated skills, passion,
commitment and have a track record of success in its areas of focus; and,
leveraging the expertise of partners around the world to assist it in the
execution of its strategy. For more information, please visit the Company's
website at www.sppirx.com. 

TopoTarget Safe Harbour 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 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 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's history of
incurring losses and the uncertainty of achieving profitability; TopoTarget's
stage of development as a biopharmaceutical company; government regulation;
patent infringement claims against TopoTarget's products, processes and
technologies; the ability to protect TopoTarget's patents and proprietary
rights; uncertainties relating to commercialization rights; and product
liability expo-sure; 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.