København, Danmark - 13. september 2011 - Topotarget A/S (NASDAQ OMX: TOPO.CO)
har i dag meddelt, at kliniske data (videnskablige resuméer) vil blive
præsenteret på The European Multidisciplinary Cancer Congress i Stockholm den
23.-27. september 2011.

Nedenfor er en liste over de videnskabelige resuméer der nu er tilgængelige på
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,3 R. 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
1Cancer Research UK Beatson Laboratories, Centre for Oncology and Applied
Pharmacology, Glasgow, United Kingdom ; 2Topotarget, Clinical Pharmacology,
Copenhagen, Denmark ; 3Topotarget, Medical Affairs, Copenhagen, Denmark ;
4Herlev Hospital, Department Oncology, Copenhagen, Denmark ; 5Royal Marsden
Hospital, Institute for Cancer Research, Sutton, United Kingdom

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-∞) relative to Bel were 16- (BelGlcU), 3- (3-ASBA), 1-
(Metbel), 1- (Belam) and 0.5-fold (Belac).

Bel metabolites did not inhibit HDAC-i activity or cell WST proliferation in
vitro. In the CAs the IC50 for Bel were 0.4 to 1.3µM. Three metabolites had
weak effect relative to Bel. The fold increase in IC50 relative to Bel was: >65
(BelGlcU), >42 (Metbel) and >114 (Belam).

Conclusions: Five major human Bel metabolites (BelGlcU, 3-ASBA, Metbel, Belam
and Belac) were identified in a Ph II study of BelCaP in pts with TCCB. Bel
metabolites were inactive in HDAC-i assays and in WST assays and had weak
activity in CA. The metabolite with highest fold exposure compared to Bel was
BelGlcU (16-fold), which was 65 fold less effective in vitro than Bel. The
present study finds that Bel metabolites do not have significant biological
effect at therapeutic relevant plasma exposure in cancer pts.


Dagens meddelelse ændrer ikke Topotargets finansielle forventninger for helåret
2011.



Topotarget A/S

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Baggrundsoplysninger

Om belinostat

Belinostat er en lovende molekyle HDAC-hæmmer, som undersøges for sin rolle i
behandlingen af en lang række solide tumorer og blodkræftsygdomme, enten alene
eller i kombination med andre aktive antikræft-midler, herunder carboplatin,
paclitaxel, doxorubicin, idarubicin, cis-retinoidsyre, azacitidin, 5-FU,
etoposid og Velcade® (bortezomib) til injektion. HDAC-hæmmere udgør en ny
mekanistisk klasse antikræftmidler, som er rettet mod HDAC-enzymerne, og de har
vist sig at: stoppe kræftcellernes vækst (herunder undertyper, der er
resistente over for lægemidler), inducere apoptose (programmeret celledød),
fremme differentiering, hæmme angiogenese (dannelse af blodkar), og
sensibilisere kræftcellerne til ikke længere at være resistente, når de
anvendes i kombination med andre antikræftmidler.

Intravenøst indgivet belinostat undersøges i øjeblikket i et pivotalstudie til
behandling af perifert T-celle lymfekræft (PTCL) og undersøges i en række
kliniske undersøgelser som en potentiel behandling af kræft med ukendt
primærtumor (CUP), kræft i æggestokkene, småcellet lungekræft, tymom,
leverkræft, bløddelssarkom, lymfekræft, AML samt myelodysplastisk syndrom
(MDS), enten alene eller i kombination med andre antikræftbehandlinger.
Konstant intravenøs infusion (CIV) evalueres i kliniske undersøgelser til
behandling af både solide tumorer og AML. Topotarget har indgået en Clinical
Trial Agreement (CTA) med NCI omkring kliniske studier med belinostat for bedre
at kunne forstå stoffets antitumoraktivitet.

Om Topotarget

Topotarget (NASDAQ OMX: TOPO.CO) er en skandinavisk-baseret international
biotekvirksomhed med hovedkontor i Danmark dedikeret til at forbedre
behandlinger mod kræft. I samarbejde med Spectrum Pharmaceuticals, Inc.
fokuserer Topotarget i øjeblikket på udviklingen i de pivotale studier af dets
førende lægemiddelkandidat, belinostat, som har vist en tydelig antineoplastisk
effekt i behandlingen af såvel blodkræftsygdomme som solide kræftsvulster.
Belinostat kan anvendes i kombination med fulde doser kemoterapi og er i
registreringsfase i PTCL (perifert T-celle lymfekræft) samt i fase II i kræft
med ukendt primærtumor (CUP). Topotargets primære kræftbehandlings-target er
HDAC. Totect® er et markedsført produkt, som er udviklet fra Topotargets
forskningsteknologi. Totect® markedsføres af selskabets egne salgsspecialister
i USA. De europæiske rettigheder til Savene® blev frasolgt i marts 2010 som
resultat af selskabets fokus på at udvikle og kommercialisere belinostat. For
yderligere oplysninger henvises til www.topotarget.com.

Topotarget Safe Harbour Statement

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forventninger til udviklingen af vores prækliniske og kliniske pipeline med
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ledelsens nuværende forventninger og er forbundet med risici og usikkerhed, som
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investorer om, at der ikke kan gives sikkerhed for, at de faktiske resultater
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eller gives udtryk for i sådanne fremadrettede udsagn som følge af forskellige
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tekniske, videnskabelige eller kommercielle årsager, som følge af problemer med
patientrekruttering eller på baggrund af nye oplysninger fra ikke-kliniske
eller kliniske studier eller fra andre kilder; succesfulde konkurrerende
produkter og teknologier; teknologisk uvished og produktudviklingsrisici;
usikkerhed omkring yderligere finansiering; Topotargets historiske underskud og
usikkerheden omkring opnåelse af lønsomhed; Topotargets udviklingsstadie som
biofarmaceutisk selskab; offentlig regulering; påstande om patentkrænkelse mod
Topotargets produkter, procedurer og teknologier; evnen til at beskytte
Topotargets patenter og immaterielle rettigheder, usikkerhed vedrørende
kommercialiseringsrettigheder samt risiko for produktansvarskrav. Vi har ingen
hensigt om og påtager os ingen forpligtelse til at opdatere eller ændre
fremadrettede udsagn, hverken som følge af fremkomsten af nye oplysninger,
fremtidige begivenheder eller på anden måde, medmindre loven kræver det.

Meddelelse nr 16-11 resumeer ESMO-ECCO.pdf