TopoTarget A/S : Belinostat abstracts at the European Multidisciplinary Cancer Congress 2011

Copenhagen, Denmark – 13 September, 2011 – Today Topotarget A/S (NASDAQ OMX: TOPO.CO) announcedthat clinical data on belinostat will be presented at The European Multidisciplinary Cancer Congress in Stockholm, 23-27 September 2011.

Below is a list of the two abstracts accepted at The European Multidisciplinary Cancer Congress http://stockholm2011.ecco-org.eu/Programme;

Abstract 6597, Monday 26 September, time: 8.00-10.00, Hall C

A phase II study of epigenetic therapy using belinostat for patients with unresectable hepatocellular carcinoma: a multicenter study of the Mayo Phase 2 Consortium (P2C) and the Cancer Therapeutics Research Group (CTRG)

W. Yeo1, H.C. Chung2, S.L. Chan1, L.Z. Wang,3R. Lim3, J. Picus4, M. Boyer5, C. Erlichman6, A.T.C. Chan1, B.C. Goh3. Department of Clinical Oncology1, Chinese University of Hong Kong, Hong Kong. Division of Haematology-Onology, Yonsei Cancer Center, Yonsei University College of Medicine, Korea2. Department of Haematology-Oncology, National University Hospital, Singapore3. Washington University, School of Medicine, St. Louis, MO, USA4. Sydney Cancer Centre, Royal Prince Alfred Hospital, Australia5. Mayo Phase 2 Consortium6.

Background: Patients with unresectable hepatocellular carcinoma (HCC) carry a dismal prognosis. Epigenetic aberrations have been reported in HCC. Belinostat is a novel, low molecular weight, histone deacetylase inhibitor. The purpose of this study was to assess the efficacy of epigenetic therapy with belinostat in patients with unresectable HCC.

Patients and methods: Major eligibility criteria included histologically confirmed HCC that is not amenable to curative treatment; ECOG£2; adequate organs functions. The belinostat dose used was 1400 mg/m2/day i.v. on day 1-5 every 3 weeks, as defined in a prior phase I study. The primary endpoint was progression-free survival (PFS) and the secondary endpoints were response rate (RR) according to RECIST and overall survival (OS). Adverse events were reported using CTCAE v3.

Results: 42 patients were accrued. Prior therapies included surgery (36%), radiofrequency ablation (7%), transarterial therapy (50%); prior systemic therapies (38%). Median follow-up was 20.0 months. Median cycle no. was 2 (range: 1-12). The PR and SD rate was 2.4% (1/42) and 45.2% (19/42) respectively. Median PFS was 2.64 months (95%C.I. 1.55-3.17) and OS was 6.60 months (95%C.I. 4.53-11.60). Grade >3 toxicities that occurred in >5% included: 4 (9.5%) abdominal pain, 4 (9.5%) hyperbilirubinemia, 4 (9.5%) raised alanine transaminase, 3 (7.1%) anemia, 3 (7.1%) vomiting, 2 (4.8%) distension, 2 (4.8%) hemorrhage, 2 (4.8%) prolonged QTc and 2 (4.8%) dehydration. One patient developed sudden death but it was determined not likely due to study medication.

Conclusions: With the majority of patients having failed prior therapy, epigenetic therapy with belinostat demonstrates tumor stabilization and is generally well-tolerated. Further studies including combinational study with other agents is warranted.

Acknowledgement: The study was sponsored by the Division of Cancer Treatment and Diagnosis, National Cancer Institute, U.S.A, and its collaborator TopoTarget.

Abstract 7105, Sunday 25 September, time: 11-12, Hall A8

Belinostat in Combination With Carboplatin and Paclitaxel (BelCaP) for Treatment of Bladder Cancer - a Pharmacokinetic Study of Exposure to Belinostat and Its Metabolites

Co-authors: R.J. Jones1, J. Tjørnelund2, K.D. Erichsen3, L. Sengeløv4, J. De Bono5

Background: Belinostat (Bel, PXD101) is a class I and II Histone DeACetylase (HDAC) inhibitor. A single arm Ph II study was conducted to evaluate the safety and activity of Belinostat, Carboplatin and Paclitaxel (BelCaP) in patients (pts) with Transitional Cell Carcinoma of the Bladder (TCCB) (n=15). A part of the study was a pharmacokinetic study of plasma exposure to Bel and its metabolites. The in vitro efficacy of belinostat and its metabolites were compared and related to plasma exposure in pts.

Materials and Methods: Pts with TCCB were treated with BelCaP every third week; Bel was given as a 1000mg/m2 30-min i.v. inf. on days 1–5 with P (175mg/m2) and subsequently Ca (AUC5) administered 2–3hrs after Bel on day 3. The plasma exposure (AUC) of Bel and its metabolites were determined. The in vitro pharmacological effect of Bel and its five major metabolites: belinostat glucuronide (BelGlcU), 3-(Anilinosulfonyl)benzene carboxylic acid (3-ASBA), methylated belinostat (Metbel), belinostat amide (Belam) and belinostat acid (Belac) were examined in a HeLa HDAC enzyme inhibition assay (HDAC-i), in WST proliferation assays and in clonogenic assays (CA). Fold differences in exposure of metabolites and belinostat (10 pts on day 3) and fold differences in in vitro efficacy of belinostat and metabolites were compared.

Results: The exposure of each metabolite relative to Bel was evaluated. The increases (molar AUC0–