To NASDAQ OMX Copenhagen A/S
Announcement No. 20-10 / Copenhagen, 21 May
2010
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

TOPOTARGET A/S ANNOUNCES BELINOSTAT ABSTRACT AT
THE 2010 ANNUAL MEETING OF THE
AMERICAN SOCIETY OF CLINICAL ONCOLOGY

•
Abstracts Now Available for Viewing at ASCO.org
•
Phase 2 Study of
Belinostat Monotherapy in Relapsed/Refractory PTCL
demonstrated 32% Objective
Response Rate 
•
Additional Information to be Provided During ASCO Annual
Meeting
Copenhagen, Denmark - 21 May 2010 - Topotarget A/S (NASDAQ OMX: TOPO)
,
announces that clinical data on belinostat will be presented at the 2010
Annual
Meeting of the American Society of Clinical Oncology (ASCO), to be held
June
4-8, 2010 at the McCormick Place Convention Center in Chicago, Illinois,
as
part of the ASCO proceedings. 
Shown below is the summary abstract on the
currently enrolling pivotal,
registrational PTCL trial being conducted under a
Special Protocol Assessment,
as well as 4 other abstracts that are now
available for viewing on the ASCO.org
website (www.asco.org). 
A Multicenter,
Open-Label Trial of Belinostat in Patients with Relapsed or
Refractory
Peripheral T-Cell Lymphoma 
•
Owen A. O'Connor - NYU Cancer Institute, New
York, NY
•
Pier Luigi Zinzani - University of Bologna, Bologna, Italy
The
study is a global, multicenter, single arm efficacy and safety study
of
belinostat monotherapy in patients with relapsed or refractory
peripheral
T-cell lymphoma (PTCL) who failed at least one prior systemic
therapy. Main
aims are to determine objective response rate and time-related
response
parameters. 
Belinostat is a hydroxamate, class I & II histone
deacetylase inhibitor
(HDACi). Pre-clinically, belinostat has a broad
antineoplastic spectrum at
sub-micromolar concentrations including T-cell
lymphoma lines. Phase 1 and 2
trials are ongoing in multiple indications and
in more than 500 patients.
Belinostat treatment was safe and well tolerated,
and the most common events
included nausea, fatigue, and vomiting. A Phase 2
study of belinostat
monotherapy in relapsed/refractory PTCL demonstrated in 19
evaluable patients
an objective response rate of 32% and a median response
duration of 268+ days.
The results led to the present pivotal trial in PTCL as
agreed with FDA under a
Special Protocol Assessment. 
Page 1 of 5
TOPOTARGET
A/S ANNOUNCES BELINOSTAT
ABSTRACT AT THE 2010 ANNUAL MEETING OF THE
AMERICAN
SOCIETY OF CLINICAL ONCOLOGY
Eligible patients have received at least one
prior systemic chemotherapy and
have histologically confirmed diagnosis of
PTCL of one of the subtypes: 
•
Anaplastic large cell lymphoma (ALK-positive
or negative),
•
ALK-negative,
•
Angioimmunoblastic T-cell
lymphoma
•
Enteropathy-associated T-cell lymphoma
•
Extranodal NK/T-cell
lymphoma
•
Nasal type,
•
Hepatosplenic T-cell lymphoma
•
Peripheral
T-cell lymphoma
•
Not otherwise specified (NOS) or
•
Subcutaneous
panniculitis-like T-cell Lymphoma
The diagnosis should be confirmed by a
positive set of T-cell markers and
negativity of B-cell markers. A pathology
panel will review all diagnosis
specimens. 
Belinostat will be administered
as a 30-minute IV infusion of 1000 mg/m2 on
days 1-5 of every 3-week cycle
until disease progression or unmanageable
treatment-related toxicities. 
As
of January 4, 2010, 19 patients have been included in the trial. The
primary
study endpoint is objective response rate (ORR). The sample size was
based on a
2-stage optimal design with a hypothesized ORR of p1=20% for B and
a minimal or
“uninteresting” ORR of p0=9%. At least 14 confirmed objective
responses in 100
evaluable patients are required to confirm a 20% target
response rate with an
alpha of 0.05 assuming a power of 90%. 
Pharmacokinetic
data will be collected to explore exposure-response
relationships. 
Monday,
June 7, 2010 - 8:00am - 12:00pm
Trials in Progress Poster Session - Special
Session, Clinical trials - S Hall A2
Abstract #TPS185: An Open-Label
Randomized Phase 2 Trial Of Belinostat (PXD101)
In Combination With
Carboplatin And Paclitaxel (BelCaP) Compared To Carboplatin
And Paclitaxel In
Patients With Previously Untreated Carcinoma Of Unknown
Primary. 
•
Karim
Fizazi - Institut de Cancerologie Gustave Roussy, Villejuif, France
•
John
Hainsworth - Tennessee Oncology Sarah Canon Research Institute, US
Treatment
options for patients with cancer of unknown primary (CUP) are
limited;
carboplatin and paclitaxel combination being one of the options.
Belinostat,
is a hydroxamate, class I and II histone deacetylase inhibitor
(HDACi) with a
broad antineoplastic activity. Phase I and II trials are ongoing
in multiple
indications and in more than 500 patients the most common adverse
events have
been nausea, vomiting and fatigue. Preclinical data shows
synergistic effect
when combined with carboplatin and paclitaxel in vitro and
in vivo. In a Phase
I study for patients with pretreated advanced solid tumors,
BelCaP was
well-tolerated and active with objective responses seen in
pancreatic and
rectal cancer patients. A patient with CUP (3 prior chemotherapy
regimens) had
disease control during 29 months of treatment. Therefore, we are
conducting a
randomized Phase 2 study (N~88) of CaP with or without belinostat
in CUP
patients. 
Randomized, global, multicenter Phase 2 trial in 19 centers.
Inclusion criteria
include: a confirmed diagnosis of CUP, no prior therapy,
ECOG PS 0-2, age > 18
years. Eligible patients are randomized to receive
either arm A or B. 
•
Arm A: BelCaP; belinostat as a 30-min i.v. infusion
once daily (1000 mg/m2)
on days 1-3, Announcement No. 20-10 Page 2 of
5
TOPOTARGET A/S ANNOUNCES BELINOSTAT
ABSTRACT AT THE 2010 ANNUAL MEETING OF
THE
AMERICAN SOCIETY OF CLINICAL ONCOLOGY
followed by belinostat 2000mg
orally once daily on days 4-5, with paclitaxel
(175 mg/m2) administered 2-3
hours following belinostat on day 3 and
carboplatin (AUC6) following directly
after paclitaxel, up to 6 cycles. From
cycle 7: belinostat 750 mg is
administered orally once daily x 14 days. 
•
Arm B: Paclitaxel (175 mg/m2)
administered day 1 and carboplatin (AUC6)
following directly after paclitaxel.
Cycles repeated every 3 weeks.
Primary endpoint is progression free survival
(PFS) and secondary endpoints
assess additional efficacy parameters and
safety. Response is evaluated
according to RECIST criteria. 33 patients have
been randomized as of
06-Jan-2009. 
Monday, June 7, 2010 -
8:00am-12:00pm
General Poster Session - Developmental Therapeutics - S Hall
A2
Abstract #2585 - Phase 1 Pharmacokinetics and Metabolic Pathway of
Belinostat
in Patients with Hepatocellular Carcinoma. 
•
L. Z. Wang, et
al.
Metabolic inactivation of several hydroxamic acid-derived histone
deacetylase
inhibitors (HDACi) involves glucuronidation. Vorinostat, a
pan-HDACi, undergoes
glucuronidation by UGT2B17. We studied the
pharmacokinetics and metabolic
pathway of belinostat (PXD101). 
In vitro
glucuronidation of belinostat was investigated; plasma
pharmacokinetics of
belinostat was studied in a phase I study in patients with
hepatocellular
carcinoma. Seventeen patients were treated with belinostat at
escalating doses
of 600 (n = 3), 900 (n = 3), 1200 (n = 6), 1400 (n = 5) mg/m2
daily by
intravenous infusion over 30 minutes for 5 days every 21 days; blood
was drawn
on day 1 before infusion, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 5 and 24
hours after
the start of infusion, plasma was isolated for determination of
belinostat and
identification of its metabolites using LC-MS/MS.
Pharmacokinetics of
belinostat was studied using non-compartmental methods. 
Using a panel of 12
UGT isoforms, UGT1A1 was found to be the predominant enzyme
for
glucuronidation of belinostat with one third of unmetabolized belinostat
left
after 1 h incubation at 37 ºC. Belinostat glucuronide had no activity
against
HONE1 cell line at 10 μM, compared to an IC50 of 1.59 ± 0.90 μM
for
belinostat. Belinostat AUC increased linearly with dose, with a mean
clearance
of 34.34 ± 10.56 L/h/m2 and terminal half-life of 2.94 ± 0.48 h.
Five
metabolites in human plasma were identified. Glucuronidation was the
most
significant pathway of belinostat metabolism; 2 alternate
biotransformation
pathways involved methylation to methylated belinostat and
reduction of
hydroxamic group to its corresponding belinostat amide. In
addition, two minor
metabolites were found to be belinostat N-glucoside and
belinostat acid.
Belinostat glucuronide increased in levels shortly after
administration,
reaching the maximum concentration at 1 h from start of
infusion. 
Phase II biotransformation played a key role on belinostat
disposition, with
UGT 1A1 likely involved in the major pathway. Further
studies should explore
the role of common polymorphisms of UGT1A1 on
belinostat disposition and
pharmacodynamics. 
Saturday, June 5, 2010 -
8:00am-12:00pm
General Poster Session - Leukemia, Myelodysplasia, and
Transplantation - S Hall
A2 
Abstract #6607 - Phase 2 Study of the Histone
Deacetylase (HDAC) Inhibitor
Belinostat for the Treatment of Myelodysplastic
Syndrome (MDS) 
•
Amanda Cashen, MD, et al.
Announcement No. 20-10 Page 3 of
5
TOPOTARGET A/S ANNOUNCES BELINOSTAT
ABSTRACT AT THE 2010 ANNUAL MEETING OF
THE
AMERICAN SOCIETY OF CLINICAL ONCOLOGY
Inhibition of HDAC can induce
differentiation, growth arrest, and apoptosis in
cancer cells. Belinostat is a
potent inhibitor of both class I and class II
HDAC enzymes. This Phase II
study was undertaken to estimate the efficacy of
belinostat for the treatment
of MDS. 
Adults with MDS (any WHO classification, plus at least 1 significant
cytopenia
if <5% bone marrow blasts) were eligible if they had ≤ 2 prior
therapies for
MDS, adequate renal and hepatic function, and ECOG 0-2. The
primary endpoint
was proportion of confirmed responses (CR, PR, and
hematologic improvement
[HI]) during the first 12 weeks of treatment. Patients
were treated with
belinostat 1000 mg/m2 as a 30 min IV infusion on days 1-5 of
a 21 day cycle for
4 cycles. Responding patients could receive additional
cycles until disease
progression or unacceptable toxicity. 21 patients were to
be enrolled in the
first stage, and if 3 or more responses were observed, an
additional 29 would
be enrolled in stage 2. 
21 patients (median age, 67
years) were enrolled, and all are evaluable.
Patients were a median 13.4
months from diagnosis (range, 0.3-210) and had bone
marrow blasts of <5%
(n=14), 5-9% (n=6), and 10-19% (n=1). 13 patients (62%)
had good risk
cytogenetics, and 7 (33%) had poor risk. 17 patients (81%) were
transfusion
dependent. Prior therapy included azacitidine (n=7) and
chemotherapy (n=8).
Patients were treated with a median 2.5 cycles (range, 1-8)
of belinostat.
There was one confirmed response - HI in neutrophils - that
lasted 2.1 months,
for an ORR of 5% (95% CI, 0.2-23). Median Overall Survival
was 14.5 months.
Median time to progression was 15.5 months. Grade 3-4
toxicities considered at
least possibly related to belinostat were: neutropenia
(n=10),
thrombocytopenia (n=9), anemia (n=5), fatigue (n=2), febrile
neutropenia
(n=1), and headache (n=1). 2 patients had Grade 2 cytokine release
syndrome
during belinostat infusion, and 2 patients had QTc prolongation.
Because the
study met the stopping rule in the first stage of enrollment, it
was closed to
further accrual. 
Although well-tolerated, belinostat does not have sufficient
efficacy to
warrant further investigation as a single agent in MDS. Supported
by NCI
N01-CM62205 
About Belinostat
Belinostat (PXD 101) is a Class I and
II HDAC inhibitor that is being studied
in multiple clinical trials as a
single agent or in combination with
chemotherapeutic agents for the treatment
of various hematological and solid
cancers. Its anticancer effect is thought
to be mediated through multiple
mechanisms of action, including the inhibition
of cell proliferation, induction
of apoptosis (programmed cell death),
inhibition of angiogenesis, induction of
differentiation, and the
resensitization of cells that have overcome drug
resistance to anticancer
agents such as platinums, taxanes and topoisomerase II
inhibitors. Belinostat
is the only HDAC inhibitor in clinical development with
multiple potential
routes of administration, including intravenous
administration, continuous
intravenous infusion and oral administration. 
Belinostat is currently in a
registrational trial, under a Special Protocol
Assessment (SPA), as a
monotherapy for relapsed or refractory Peripheral T-Cell
Lymphoma (PTCL), an
indication for which it has been granted Orphan Drug and
Fast Track
designation by the U.S. Food and Drug Administration. The Company
currently
plans to file a New Drug Application (NDA) in 2011. Belinostat is
also under
investigation in a randomized Phase 2 trial, as a combination
therapy with
carboplatin and paclitaxel, for cancer of unknown primary (CUP).
Additionally,
the National Cancer Institute is currently conducting several
clinical trials
of Belinostat in a variety of hematological and solid tumors,
both as
monotherapy as well as combination therapy. 
Announcement No. 20-10 Page 4 of
5
TOPOTARGET A/S ANNOUNCES BELINOSTAT
ABSTRACT AT THE 2010 ANNUAL MEETING OF
THE
AMERICAN SOCIETY OF CLINICAL ONCOLOGY
Announcement No. 20-10 Page 5 of
5
Topotarget A/S
For further information, please contact:
Francois Martelet,
CEO: Direct: +45 39 17 94 99; Mobile: +45 31 36 83 41
Anders Vadsholt, CFO:
Direct: +45 39 17 83 45; Mobile: +45 28 98 90 55
Background information
About
Topotarget
Topotarget (NASDAQ OMX: TOPO) is an international biotech company
headquartered
in Denmark, dedicated to improve 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 currently
in a pivotal
trial within PTCL (peripheral T-cell lymphoma). Topotarget's key
cancer drugs
target HDAC, NAD+, mTOR, Fas ligand and topoisomerase II. 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
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 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.