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.


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Investor Nyhed nr. 02-14 Belinostat resumé på American Association for Cancer Research 2014.pdf