København, Danmark - 19. maj 2011 - Topotarget A/S (NASDAQ OMX: TOPO.CO) har i
dag meddelt, at kliniske data (videnskablige resuméer) vil blive præsenteret på
ASCO's 2011 årsmøde (American Society of Clinical Oncology). Mødet afholdes i
Chicago, the McCormick Place Convention Center fra den 3. juni til den 7. juni
2011.Neden for er en liste over de videnskabelige resuméer der der nu er
tilgængelige for gennemsyn på ASCO's hjemmeside (www.asco.org).


A phase I and pharmacodynamic (PD) study of the histone deacetylase (HDAC)
inhibitor belinostat (BEL) plus azacitidine (AZC) in advanced myeloid
malignancies.


Abstract No: 6521


Session: Leukemia, Myelodysplasia, and Transplantation. Type: Poster Discussion
Session, Time: Friday June 3, 2:00 PM to 6:00 PM. Location: McCormick Place
E450b

Discussion Time: Friday June 3, 5:00 PM to 6:00 PM. Location: McCormick Place
Arie Crown Theater.


Author(s): O. Odenike, L. A. Godley, J. Madzo, T. Karrison, M. Green, A. S.
Artz, R. J. Mattison, K. W. L. Yee, M. Bennett, N. Fulton, G. Koval, G.
Malnassy, R. A. Larson, M. J. Ratain, W. Stock; The University of Chicago,
Chicago, IL; University of Wisconsin, Madison, WI; Princess Margaret Hospital,
Toronto, ON, Canada.


Abstract:


Background: We hypothesized that targeting two mechanisms of epigenetic
silencing with a potent HDAC inhibitor BEL plus the DNA methyltransferase
inhibitor AZC would be additive or synergistic with regard to transcriptional
de-repression and up-regulation of specific target genes.


Methods: Part 1 of the study was a dose escalation phase to establish the MTD
of BEL in combination with a fixed dose of AZC. 3 to 6 pts were enrolled per
dose level in the absence of a DLT or until the 1000mg/m2 dose level of BEL was
attained. AZC was given at a dose of 75mg/m2/d SC on days 1-5, with escalating
doses of BEL given IV over 30 minutes on the same days in a 28 day cycle. In
part 2, pts were randomized during cycle 1 to AZC alone, or BEL/AZC at the
established MTD of BEL. Part 2 was designed to evaluate the relative
contribution of BEL to the combination, based on change in PD variables
analyzed at day 5 of therapy in comparison to baseline, in cycle 1. In
subsequent cycles all pts could receive BEL/AZC.

Results: 56 pts were enrolled, part 1 (n=24), part 2 (n=32). Median age 68,
range (42-83). AML de novo=53% t- AML/MDS=18%, MDS/CMML=27%, PMF=2%; 68% had
primary refractory or relapsed disease, 43% had poor risk cytogenetics. In part
1, dose escalation was feasible up to the 1000mg/m2 dose level of BEL, without
first course DLT. In part 2, 18 pts (9 in each arm) had marrow samples at
baseline and at day 5 for q-RT-PCR analysis for p21, MDR1 and HIST1H3H
transcript levels. At day 5, MDR1 was significantly upregulated in the BEL/AZC
arm when compared with AZC alone arm (p=0.0089), in contrast to p21 and
HIST1H3H which were not significantly different between the 2 arms. There
were18 responses (CR=6, marrow CR =2, PR= 1, HI-P=7, HI-N=2); 13 of these
occurred at the 1000mg/m2 dose level of BEL.


Conclusions: The combination of BEL and AZC is feasible, responses have been
observed in several pts at the RP2D of 1000mg/m2 of BEL plus 75mg/m2 AZC. A
significant upregulation in MDR1 was observed in the BEL/AZC arm at day 5
compared with the AZC alone arm, suggesting a relative biologic contribution of
BEL to the combination. The clinical correlates of these observations require
evaluation in the context of a larger trial.



Management of thymic epithelial tumors (TETs) at the National Cancer Institute
(NCI).


Abstract No: e17511


Publication-only abstracts (abstract number preceded by an "e"), published in
conjunction with the 2011 Annual Meeting but not presented at the Meeting, can
be found online only. The publication-only abstracts are not included in the
print or USB versions of the ASCO Annual Meeting Proceedings Part I, but they
are citable to the Journal of Clinical Oncology.


Author(s): A. Rajan, R. J. Kelly, A. Lopez-Chavez, C. A. Carter, E. Szabo, B.
Scepura, M.

J. Manu, A. W. Berman, G. Giaccone; National Cancer Institute, Bethesda, MD.


Abstract:


Background: TETs are very rare anterior mediastinal tumors.


Methods: We performed a retrospective review of patients (pts.) with TETs
presenting to the NCI for enrollment in ongoing clinical trials,
standard-of-care therapy or a second opinion.


Results: Seventy-three pts. were seen between 12/2007 and 12/2010; 43 males
(41%), median age at diagnosis: 48 years (range, 17 - 81). Fifty-four pts. were
Caucasian (74%), 7 (10%) African-American, 8 (11%) Asian and 4 (6%) Hispanic.
Histology: B1 5 (7%), B2 13 (18%), B2/B3 1 (1%), B3 9 (12%), thymic carcinoma
(TC) 35 (48%), atypical carcinoid 2 (3%) and unclassified thymoma 8 (11%).
Fifty pts. were enrolled in clinical trials: 28 on a phase II study of the HDAC
inhibitor, belinostat (B), 27 on a phase II study of the IGF -1R inhibitor
cixutumumab (C) (including 10 previously on B), 3 on a phase I study of
chemotherapy (PAC) plus B and 2 on a phase II study of the cyclin-dependant
kinase inhibitor PHA-848125AC. Median number of previous systemic therapy
regimen that had been administered was 2 (range, 0-10). Forty-three pts. (59%)
had extra-thoracic metastases; liver, bone and lymph nodes were the most common
sites. Fourteen pts. (19%) had at least one autoimmune disease; myasthenia
gravis (10%) was the most common. Three out of six pts. with TC with
neuroendocrine features had Cushing's syndrome. Eleven pts. (15%) had
opportunistic infections including shingles (8%) and candidiasis (4%).
Forty-eight pts. On clinical trials were evaluable for response: B: 2PR, 18SD,
8PD; C: 1PR, 16SD, 8PD; PACB: 1PR, 2SD; PHA: 2SD. Median survival for all pts.
was 117 months (T - not reached; TC - 56 months). Among 28 pts. enrolled on B,
the only clinical predictor of response and survival was presence of
intra-thoracic disease only. Of 12 tumors (B1-1, B2-2, B3-1, C-7, atypical
carcinoid-1) evaluated for overexpression of HER2 by IHC, none was positive.
One patient with TC had a c-KIT mutation in exon 11.


Conclusions: Histologic diagnosis of thymoma and the presence of intra-thoracic
disease only predicts for longer survival in pts. with TETs. Targeted drugs can
induce prolonged disease stabilization and few responses in heavily pretreated
patients. Molecular profiling of tumors will be necessary in order to advance
the field.



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-targets er
HDAC, NAD+ og topoisomerase II. 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

Denne meddelelse kan indeholde fremadrettede udsagn, herunder udsagn om vores
forventninger til udviklingen af vores prækliniske og kliniske pipeline med
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investorer om, at der ikke kan gives sikkerhed for, at de faktiske resultater
eller forretningsforhold ikke vil afvige væsentligt fra hvad, der forudsiges
eller gives udtryk for i sådanne fremadrettede udsagn som følge af forskellige
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flere af Topotargets udviklingsprogrammer ikke skrider frem som planlagt af
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. 11-11 Videnskabelige belinostat resuméer på ASCOs årsmøde 2011.pdf