Til NASDAQ OMX Copenhagen A/S
Investor Nyhed nr. 02-14 / København, 6. marts 2014

Kliniske data (videnskabeligt resumé) vil blive præsenteret på 2014-årsmødet for American Association for Cancer Research (AACR) den 5.-9. april 2014.

Nedenfor ses det videnskabelige kliniske resumé, der nu er tilgængeligt på AACR's hjemmeside (http://www.aacr.org/ ).

Abstract number: CT207. Presentation time: Monday, April 07, 2014, 8:00 AM -12:00 PM. Location: Hall A-E, Poster Section 38. Poster board number: 7.

Pharmacokinetic analysis of the HDAC inhibitor belinostat (PXD-101) and metabolites in patients with hepatic dysfunction

Brian Kiesel1, Robert Parise1, Yan Lin1, Deborah Allen2, Guru Reddy3, Shanta Chawla3, Richard Piekarz4, Percy Ivy4, Shivaani Kumar2, Jan H. Beumer1. 1Univ. of Pittsburgh Cancer Inst., Pittsburgh, PA; 2NIH/NCI, Bethesda, MD; 3Spectrum Pharmaceuticals, Irvine, CA; 4NIH/NCI, Rockville, MD.

Introduction: Histone deacetylases (HDAC) are frequently deregulated in human cancers and their inhibition allows re-expression of silenced genes. Belinostat is an HDAC inhibitor with in vitro and in vivo activity in multiple malignancies, currently in phase II trials. We report the pharmacokinetics of belinostat and metabolites in patients enrolled in a phase I liver dysfunction trial currently being conducted and led by the NCI.

Methods: Patients enrolled into the study were assigned to varying cohorts depending on their level of hepatic dysfunction (normal=N, mild=H1, moderate=H2, and severe=H3). All patients were given a 30-minute infusion at 400 mg/m2 on cycle 1 day -7. Heparinized plasma samples were collected prior to infusion, 15 and 25 min after start, and 5, 10, 15, 30, 60, 90, 120, 240, 360, 480, and 1440 minutes after infusion. Patients from the NCIDTC had samples collected and these were quantitated by a previously validated assay for belinostat, belinostat-glucuronide, methyl-belinostat, M21, M24, and M26. Pharmacokinetic parameters were derived non-compartmentally with PK Solutions. Metabolic ratios were calculated as a measure of metabolic fate.

Results: 15 patients (N=2, H1=10, H2=2, H3=1) had useable pharmacokinetic data. Observed belinostat Cmax (N=21.1±4.9, H1=55.8±78.0, H2=23.0±7.2, H3=23.1 µg/mL) and belinostat AUC0-inf (N=806±294, H1=1308±996, H2=702±82, H3=780 µg/mL•min) did not reveal any trends with dysfunction cohort. Metabolic AUC0-inf ratios of belinostat to the various metabolites also did not appear to change with dysfunction cohort.

Conclusion : Liver function does not appear to affect the pharmacokinetics or metabolic fate of belinostat. Analysis of additional subjects is on-going. The results of this study will facilitate optimal dosing for patients with liver dysfunction.

Topotarget A/S

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Topotarget (NASDAQ OMX: TOPO) er et skandinavisk biofarmaceutisk selskab med hovedsæde i København. Selskabet beskæftiger sig med klinisk udvikling og registrering af onkologiprodukter. Topotarget fokuserer i samarbejde med Spectrum Pharmaceuticals, Inc. på udviklingen af dets førende lægemiddelkandidat, belinostat, som har vist positive resultater i behandling af blodkræftsygdomme og solide kræfttumorer opnået ved både enkeltstof- og kombinationsbehandling. For yderligere oplysninger henvises til www.topotarget.com.

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