Positive SPA reply from the FDA for TopoTarget's pivotal trial with belinostat in PTCL

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

To OMX Nordic Exchange Copenhagen
Announcement No. 27-08 / Copenhagen, September 5, 2008


Positive SPA reply from the FDA for TopoTarget's  pivotal trial with belinostat
in PTCL 

- Update on the regulatory strategy for belinostat in PTCL-

Copenhagen, Denmark - September 5, 2008 - TopoTarget A/S (OMX: TOPO) announced
that a positive reply from the FDA was received on a Special Protocol
Assessment (SPA) for a phase III trial for belinostat in PTCL (Peripheral
T-Celle Lymphoma). This pivotal trial is to enroll approximately 120 patients
and is to begin in Q4 2008. 
In June Fast Track designation was granted for the development of belinostat in
this indication which supports TopoTarget's rapid market entry strategy. There
is currently no standard therapy approved for PTCL. 

“This is very good news. We can now move belinostat into a pivotal phase III.
With the SPA in place we have agreed on a design for our pivotal phase III
trial with the FDA which will begin in Q4 of this year. In addition with the
FDA's Fast Track designation received in June for the PTCL indication we can
continue with our strategy of rapid market entry for belinostat in an area with
a high unmet medical need.” Said Professor, Peter Buhl Jensen, MD, CEO of
TopoTarget. 

Design
The phase III trial is an open-label, multicenter, single arm efficacy and
safety trial in patients with relapsed or refractory peripheral T-cell lymphoma
who have failed at least one prior systemic therapy. Approximately 120 patients
(100 evaluable patients) will be enrolled. Patients will be treated with 1000
mg/m2 belinostat administered as a 30 minute IV infusion on days 1-5 of every
3-week cycle until there is disease progression or unmanageable
treatment-related toxicities. 

Rational
Belinostat is a small molecule class I and II histone deacetylase inhibitor
(HDACi). HDACi's modulate gene expression within tumor cells, including tumor
suppressor genes, leading to G1 and G2/M cell cycle arrest, induction of
apoptosis (programmed cell death), inhibition of angiogenesis, immune
modulation, and promotion of cellular differentiation. 
Clinical activity of belinostat has been observed in an ongoing Phase II trial
of belinostat monotherapy in patients with recurrent or refractory cutaneous
(CTCL) or peripheral T-cell lymphoma (PTCL). Efficacy is being analyzed
separately in PTCL and CTCL patients. In 11 patients evaluable for response in
the PTCL arm, 2 durable complete responses (CR) and 4 Stable Diseases (SD) have
been observed as announced at ”10th International Conference on Malignant
Lymphoma” in Lugano in June. In both arms of the study, the objective response
rate in the first stage has met the criteria for expansion to the second stage
of a Simon 2-stage design. 

Objectives and methods of evaluation
The primary study endpoint will be objective response rate (ORR). Objective
response is complete response (CR) or partial response (PR) based on
independent radiology review. 
Secondary objectives of the study are to determine: safety of belinostat
monotherapy, time to response, duration of response, time to progression (TTP),
progression-free survival (PFS), one-year progression-free rate, one-year
survival rate and overall survival (OS). 

Today's news does not change TopoTarget's full-year financial guidance for 2008.

TopoTarget  A/S

	
For further information, please contact:

Ulla Hald Buhl 		Telephone	+45 39 17 83 92
Director IR & Communications		Mobile	+45 21 70 10 49

Background information

About Periferal T-Cell Lymphomas (PTCL)
PTCL represent approximately 10% of all non-Hodgkin's lymphomas (NHL) in
Western populations and are associated with a poor prognosis. Most patients
with PTCL relapse after initial treatment with cytotoxic agents, and 5-year
survival is less than 30%. 
T-cell Non Hodkins Lymphomas, to which PTCL belongs, are associated with a
poorer outcome and survival compared to the B-cell lymphomas. The primary
response rate for all PTCL subtypes remains at less than 60%, with nearly all
patients relapsing. Median survival of all PTCL patients (excluding a few
subtypes) is approximately 3-4 years, with a 5-year survival of less than 30%. 
There are currently no therapies approved specifically for PTCL. Primary
treatment for most subtypes of PTCL remains anthracycline-based regimens,
predominantly the combination of cyclophosphamide, doxorubicin, vincristine and
prednisone (CHOP). With the exception of ALK-positive ALCL, PTCL subtypes
respond poorly to these regimens. The use of radiotherapy, with or without
chemotherapy, is preferred as front line treatment of extranodal NK/T-cell
lymphoma. The majority of patients with PTCL will relapse after primary
therapy. A number of chemotherapy regimens are used for salvage therapy.
However, there is currently no consensus regarding the optimal treatment
approach for PTCL salvage therapy. 

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,
azacitidine 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 currently being evaluated in multiple clinical trials
as a potential treatment for cutaneous and peripheral T-cell lymphomas, B-cell
lymphomas, AML, mesothelioma, soft tissue sarcoma, MDS, and liver, colorectal,
and ovarian cancers, either alone or in combination with anti- cancer
therapies.  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 Trail 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.  In May 2005, TopoTarget announced the signing of 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 is founded and run by clinical cancer specialists
and combines years of hands-on clinical experience with in-depth understanding
of the molecular mechanisms of cancer. Focus lies on highly predictive cancer
models and key cancer targets (including HDACi, NAD+, mTOR, FasLigand and
topoisomerase II inhibitors). TopoTarget has a broad cllinical pipeline with 9
products in development, including 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. 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. 

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.