To NASDAQ OMX Copenhagen A/S
Announcement No. 15-12 / Copenhagen, September 17, 2012
Copenhagen, Denmark – September 17, 2012 – Today Topotarget A/S (NASDAQ OMX: TOPO) announced that clinical data on belinostat will be made public at the 2012 ESMO Congress’ homepage, www.esmo.org, today September 17, 2012.
Shown below is the poster abstract with results from the phase I/II clinical trial of belinostat (PXD101) in combination with idarubicin in patients with acute myeloid leukemia (AML) (PXD101-CLN-15) that will be made public today on the ESMO Congress’ homepage. The poster focuses on investigations made to identify which patient subgroups that could potentially benefit from belinostat treatment.
- Favorable impact on mainly intermediate cytogenetic risk AML can be predicted by gene expression profiling - Results of a phase I/II trial of belinostat in combination with idarubicin in AML.
Belinostat (Bel), a histone deacetylase inhibitor (HDACi), has demonstrated effective cell killing in leukemic cells and shows a synergistic effect in combination with anthracyclines in vitro. A favorable impact on the dismal clinical course of acute myeloid leukemia (AML) was suggested (Schlenk et al. ASH 2008). Recently, the phase I/II trial assessing the efficacy and safety of two schedules of Bel in patients unfit for intensive induction therapy confirmed anti-leukemic effect both of Bel alone and in combination with idarubicin (ClinicalTrials.gov ID: NCT00878722).
Among the results, we evaluated the role of cytogenetic aberrations on response to Bel therapy in 41 patients (pts.), of whom cases with intermediate risk cytogenetics in trend responded better to Bel than patients with high risk cytogenetics (p=0.14). In the dose-escalation trial, five complete remissions (CR) and two partial remissions (PR) were observed in 25 AML pts. (28%) with low/intermediate risk cytogenetic aberrations, whereas no CR and two PR were seen in 16 high-risk AML pts. (13%).
Gene expression profiling based on 13 pts. (four CR+PR and nine PD) revealed a strong gene expression pattern associated with the response to Bel. MLL, a gene well-known to be involved in epigenetic deregulation, was among the top 20 strongest correlations. Furthermore, differential expression of TP53 was also of special interest as histone deacetylases have been shown to modulate p53 transcriptional activity. In accordance, gene ontology class comparison analysis showed a significant enrichment of categories associated with epigenetic regulation such as “histone methyltransferase activity” and “histone deacetylase activity”. In addition, the respective gene expression pattern harbored predictive information as based on an in vitro cell line derived predictor a blinded Bel response prediction was feasible.
A trend indicating the potential association of Bel response and intermediate risk cytogenetics AML has been found. High-risk AML cases might also benefit from an epigenetic treatment approach with an HDACi. Further randomized studies are warranted to explore the benefit of Bel in pts. with AML.
Axel Mescheder, Chief Medical & Development Officer, says, “This phase I/II trial investigates the explored efficacy of belinostat in combination with dose escalation idarubicin in patients with AML. Belinostat was administered either as the standard regimen (30-min IV infusion 1000 mg/m2 belinostat days 1-5 every 3 weeks) or continuous IV infusion (CIV) of 25-1000 mg/m2/day belinostat day 1-2 every 2 weeks. The study showed anti-leukemic activity in the standard regimen (objective response rate 17%) as well as in CIV regimens (objective response rate 31%). The results presented at ESMO indicate that patients with AML that could potentially benefit from belinostat treatment may be identified using gene expression profiling and karyotyping. This is important knowledge for the future clinical development of belinostat”.
Topotarget A/S
For further information, please contact:
Anders Vadsholt, CEO - Direct: +45 39 17 83 45; Cell: +45 28 98 90 55
Axel Mescheder, CMDO – Direct: +45 39 17 83 14; Cell: +45 51 55 71 66
Background information
About Topotarget
Topotarget (NASDAQ-OMX: TOPO) is an international biopharmaceutical company headquartered in Copenhagen, Denmark, dedicated to clinical development and registration of oncology products. Topotarget focuses, in collaboration with Spectrum Pharmaceuticals, Inc., on the development in pivotal studies of its lead drug candidate, belinostat, which has shown positive results as a monotherapy treating hematological malignancies and positive results in solid tumors. Belinostat may be used in combination with full doses of chemotherapy, and is in a pivotal trial within PTCL (peripheral T-cell lymphoma). For more information, please refer to www.topotarget.com.
Topotarget A/S Safe Harbor 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 A/S 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 A/S 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 A/S' history of incurring losses and the uncertainty of achieving profitability; Topotarget A/S' stage of development as a biopharmaceutical company; government regulation; patent infringement claims against Topotarget A/S' products, processes and technologies; the ability to protect Topotarget A/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.
