Initiation of NCI-sponsored Phase 1 study of Belinostat in combination with Cisplatin and Etoposide for Small Cell Lung Cancer and Other Advanced Cancers

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 - August 17, 2009 - TopoTarget A/S (OMX: TOPO) announced
today the initiation of patient dosing in a Phase 1 study for the combination
of 48 hours continuous intravenous (IV) infusion of belinostat with standard
doses of cisplatin and etoposide in a three week cycle for the treatment of
patients with small cell lung carcinoma (SCLC) and other advanced cancers. The
study is sponsored by the Cancer Therapy Evaluation Program at the National
Cancer Institute (NCI, US) under a Clinical Trials Agreement with TopoTarget
for the development of belinostat. 


The Phase 1 clinical trial is being led by Susan Bates, M.D. and Richard
Piekarz, M.D., at the Medical Oncology Branch/CCR/NCI in Bethesda, MD.  The
protocol is open to all patients with recurrent or advanced cancer for whom
standard chemotherapy offers no curative potential. The trial will initially
enroll up to 36 patients in order to establish the maximum tolerated dose (MTD)
and then an additional cohort of SCLC patients will be treated at the defined
MTD. 

“We are very happy for the strong continued support from the NCI for the
belinostat programme” said Professor Peter Buhl Jensen, CEO of TopoTarget.
”This new trial builds on the preclinical data generated by the NCI and
TopoTarget that demonstrates synergy in experiments with belinostat in
combination with cisplatin and etoposide in SCLC cell lines. This study may
provide the basis for a new rational therapeutic opportunity to offer SCLC
patients.” 

The study is designed to escalate the dose of belinostat administered as a 48
hour continuous intravenous (IV) infusion on days 1 and 2, combined with IV
infusion of cisplatin on day 2 and etoposide IV daily x 3 on days 2-4 given
every 3 weeks for no more than 6 cycles. 

The primary objective of the study is to determine a safe and tolerable phase 2
dose for the combination of belinostat with cisplatin and etoposide. Secondary
objectives will include an analysis of biomarkers involved in histone
deacetylase inhibition and evaluation of tumor response in SCLC patients. 

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 II 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 I clinical trial for patients with advanced solid tumors and lymphomas.
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. 


About Small Cell Lung Cancer
Lung cancer is the leading cause of death worldwide, causing more than a
million deaths annually. In 2008, the estimated number of new lung cancers in
the US will be approximately 215,020, with roughly 12-13% of the cases being
small cell lung cancer (SCLC) SCLC are commonly assosiated with smoking. 
SCLC shows exquisite initial sensitivity to many chemotherapies and radiation
therapy but despite that have an aggressive clinical course. Nearly all
patients develop resistance to anticancer agents and relapse locally or more
commonly systemically. Untreated SCLC has a median survival of 2-4 months after
the diagnosis. Reports of expanded survival between 7 and 18 months have been
published for these patients when treated. For patients with extensive disease
the standard care is 80-100mg/m2 cisplatin on day 1 and 80-120mg/m2 etoposide
on days 1,2 and 3.