Belinostat and Velcade® is well tolerated in combination - Encouraging data from a phase 1 study presented at the AACR/NCI/EORTC Molecular Targets and

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 - November 17, 2009 - TopoTarget A/S (OMX: TOPO) announced
today that phase 1 data from a National Cancer Institute (NCI)-sponsored study
was presented at the AACR/NCI/EORTC Molecular Targets and Cancer Therapeutics
Conference 2009. In the laboratory there is strong synergy when combining
belinostat and bortezomib (Velcade®). Drugs supporting each others' activity
are eagerly sought for, especially if they can be given safely in full doses.
The study was designed to determine the maximum tolerated dose (MTD) and to
evaluate the safety and pharmacokinetic (PK) behaviour of the combination of
belinostat and bortezomib. It was concluded that belinostat and bortezomib is
well tolerated in combination with a tolerable toxicity profile and no evidence
of pharmacological interactions. Four patients have maintained stable disease
for 4-6 cycles of therapy. 

To date, 26 patients have been enrolled in the study. Twenty-two patients were
evaluable for toxicity and received a total of 58 treatment cycles; median 2
(range 1-6). At the highest dose level, dose limiting toxicity (DLTs) included
grade 4 thrombocytopenia and grade 4 fatigue. Most adverse events (AEs) have
been mild to moderate. Grade 1-2 AEs include anorexia, acute infusion reaction,
fatigue, nausea, neutropenia (1), pain, phlebitis, thrombocyctopenia, and
vomiting. Grade 3 AEs include anorexia, dehydration, fatigue, nausea, vomiting,
hypoalbuminemia, and elevation of alkaline phosphatase. Analysis of belinostat
pharmacokinetics (PK) demonstrates no statistical differences in the parameters
between days 1 (belinostat only) and 2 (belinostat + bortezomib). Doses of
belinostat from 600 to 1000 mg/m2 result in dose-proportional increases in drug
exposure. Four patients have maintained stable disease for 4-6 cycles of
therapy. 

Conclusions: Belinostat and bortezomib is well tolerated in combination with a
tolerable toxicity profile and no evidence of pharmacological interactions.
Accrual is ongoing at the MTD (belinostat: 1000 mg/m2 - bortezomib: 1.3 mg/m2). 

“Belinostat and Velcade® are synergistic in all our laboratory models. We now
know how that full doses of belinostat can be given with full Velcade® doses.
This promising combination can now be tested in larger populations. Without
NCI's support and sponsorship we probably would not have had these promising
results today,” said MD, Professor Peter Buhl Jensen, CEO of TopoTarget.
“Belinostat may become an important treatment alone or may be part of an
effective combination treatment as the safety profile of belinostat allows it
to be combined in full dose with conventional and novel therapies like
Velcade®”. 

Combination therapy with drugs having different mechanisms of action is used in
order to attack the cancer cell and potentially increase response rates. In
addition to the benefit obtained with the drug used as a single agent,
belinostat has an advantage in that it exhibits little dose limiting bone
marrow toxicity which often results in dose reductions in many chemotherapy
combinations. 
Today's news does not change TopoTarget's full-year financial guidance.


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.
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
and nonclinical studies on belinostat in order to better understand its
anti-tumor activity and to provide supporting information for clinical trials.