Positive results of the initial phase II study with belinostat in PTCL and CTCL presented at ASH

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

-Results support the registration plan in PTCL with an
 increased response rate in PTCL of 32%-



Copenhagen, Denmark - December 8 2009 - TopoTarget A/S (OMX: TOPO) has
announced that positive data from a study of belinostat given as monotherapy
1000 mg/m2/daily for 5 days every 3-weeks for the treatment of Peripheral
T-Cell lymphoma (PTCL) and Cutaneous T-Cell lymphoma (CTCL) was presented at
the 51st Annual Meeting of American Society of Haematology (ASH) 2009, 5-8
December in New Orleans, US. The study has finalized recruitment and enrolled a
total of 53 patients including 19 and 29 evaluable patients with a diagnosis of
PTCL and CTCL respectively. Efficacy data on PTCL shoved an objective response
rate of (ORR) of 32% with 6 responding patients out of 19: 2 patients had
Complete Response (CR) and 4 had Partial Response (PR). Furthermore an
encouraging median response duration of +8.9 months was seen. Initial data from
this study led TopoTarget to initiate its pivotal study in PTCL in following a
Special Protocol Assessment (SPA) procedure and Fast Track agreement with the
FDA. An Orphan Drug designation has been granted to belinostat in T-cell
lymphomas by the FDA. 

“The anti neoplastic effect of this new HDAC inhibitor, belinostat, is very
encouraging”, says Dr Foss, Yale University, New Haven, CT, US. “We have seen a
very significant objective response rate in this difficult to treat population
of previously treated PTCL patients and the treatment has been well tolerated.” 

“Importantly these new data support the company's development plan for PTCL.”
said MD, Professor Peter Buhl Jensen, CEO of TopoTarget. “There is a big unmet
medical need in this disease and with response rates of 32% for PTCL including
complete remissions - and since side effects from belinostat are mild and
different from side effects from standard chemotherapeutics - belinostat has a
huge potential. These and other clinical data indicate that belinostat can
become an important anticancer treatment both as single drug and as a new
component in combination therapy to further increase response rates for cancer
patients” Professor Peter Buhl Jensen further commented. 

The study:
Phase II open-label trial of belinostat (PXD101) in patients with recurrent or
refractory Peripheral or Cutaneous T-Cell Lymphoma 
The primary study objective was objective response rate for belinostat
monotherapy in CTCL and in PTCL. Included patients should have received at
least one prior line of systemic therapy. Patients were treated with belinostat
administered at 1000 mg/m2, as a 30-min IV infusion once daily on days 1-5 of a
21-day cycle. 

Results: The efficacy population for PTCL included 19 patients. These patients
had received a median of 2 prior systemic treatment regimens (range 1-10
regimens) and 81% had Stage III or IV disease. Responses (complete/partial
responses; CR/PR) were observed in 6 patients and stable disease (SD) was
demonstrated in 4 further patients, indicating a response rate of 32% according
to RECIST criteria and a disease control rate (CR/PR/SD) rate of 53% based on
the current preliminary data as patients are still on follow-up. Median
duration of response (CR/PR) is currently +8.9 months, and up to +28.2 months.
Median duration of stable disease (SD) is currently +4.4 months, and up to +7.8
months. Three patients with CR/PR, have not yet experienced progressive disease
and thus median durations of CR/PR can increase by longer follow-up time. 

The efficacy population for CTCL included 29 patients. These patients had
received a median of 3 prior systemic treatment regimens (range 1-9 regimens)
and 18 of them had Stage III or IV disease. 

Responses (complete/partial responses; CR/PR) were observed in 4 patients and
stable disease (SD) was demonstrated in 18 further patients, indicating a
response rate of 14% and a disease control rate (CR/PR/SD) rate of 76% based on
the current preliminary data. Median duration of response (CR/PR) is 9.1
months, and up to +15.6 months. Median duration of stable disease (SD) is
currently +1.5 months, and up to 4.2 months. One patient with CR and five
patients with SD have not yet experienced progressive disease and thus median
duration of SD can increase by longer follow-up time. 

The short time to response noted in patients with CTCL, median 16 days (range
14-35 days), is a promising finding. In addition significant pruritus relief
was seen in 7 out of 15 pruritus-evaluable patients (i.e. patients with
significant pruritus at baseline). The time to significant pruritus relief was
from 13-154 days, median 46 days). 

Belinostat monotherapy at 1000 mg/m2/daily for 5 days in a 3-weekly cycle is
safe and well-tolerated in previously treated patients with PTCL and CTCL with
the most frequent any grade drug-related adverse event being: nausea (50%),
injection site reaction (14%), vomiting (24%), anorexia (6%) and fatigue (10%).
Belinostat had only mild hematological toxicity (no grade 4 shift from baseline
anemia, neutropenia or thrombocytopenia, and grade 3 was only 4% for
neutropenia, 2% for thrombocytopenia, and 0% for anemia) and a minimal impact
on cardiac conductivity (e.g. no grade 3 QTc-prolongation was noted in
approximately 700 ECGs analyzed by a central laboratory). 



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, 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.
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 These NCI-sponsored clinical
studies are being conducted under a Clinical Trials Agreement with TopoTarget.
Furthermore TopoTarget has a Cooperative Research and Development Agreement
(CRADA) with the NCI to conduct preclinical 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
a pivotal trial 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. 

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about our expectations of the progression of our preclinical and clinical
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