København, Danmark - 9. november 2011 - Topotarget A/S (NASDAQ OMX: TOPO.CO)
har i dag meddelt, at kliniske data (videnskablige resuméer) vil blive
præsenteret på The American Society of Hematology's (ASH) årsmøde nr. 53
10.-13. december 2011 i San Diego.



Nedenfor er en liste over de to videnskabelige kliniske resuméer, der nu er
tilgængelige på http://ash.confex.com/ash/2011/webprogram/


“Vi er tilfredse med de opnåede kliniske resultater, og især den fordelagtige
bivirkningsprofil for oral administreret belinostat (abstract 3710) og som
intra-venøs injektion i kombination med bortezomib (abstract 2598)” siger Axel
Mescheder, MD, CDMO. Han fortsætter: ”At få 4 videnskablige resuméer
præsenteret på dette vigtige videnskabelige møde bekræfter vores entusiasme og
dedikerede arbejde i forbindelse med udviklingen af belinostat inden for
blodkræft”.


Dagens meddelelse ændrer ikke Topotargets finansielle forventninger for helåret
2011.


Abstract 3710: Session: 624. Lymphoma - Therapy with Biologic Agents, excluding
Pre-Clinical Models: Poster III, Monday, December 12, 2011, 6:00 PM-8:00 PM,
Hall GH (San Diego Convention Center)

Preliminary Results of An Ongoing Phase I Trial of Oral Belinostat a Novel
Histone Deacetylase Inhibitor in Patients with Lymphoid Malignancies

Jasmine M. Zain, MD1, Francine M. Foss, MD2, Catherine S. Diefenbach, MD3,
Daniel Petrylak, MD4*, Ameet Narwal1*, Ellen Neylon, NP, RN, BSN, OCN5*, Poul
Knoblauch6* and Owen A. O'Connor, MD, PhD7

1Hematology/Oncology, NYU Langone Medical Center, New York, NY
2Yale Medical Oncology, New Haven, CT
3New York University Cancer Institute, New York University Langone School of
Medicine, New York, NY
4Oncology, Columbia University, New York, NY
5Nursing, New York University Langone Medical Center, New York, NY
6TopoTarget, Copenhagen, Denmark
7Department of Medicine, NYU Cancer Institute, NYU Langone Medical Center, New
York, NY


Background: Belinostat (Bel) is a pan class I/II histone deacetylase inhibitor
with broad preclinical activity. A phase I study of oral Bel in patients (pts)
with solid tumors identified a maximum tolerated dose (MTD) of 750 mg orally
(PO) daily on days (d) 1-14, of an every 21 day cycle. An allowance for
intra-patient dose escalation was permitted as long as the higher dose level
was deemed safe and not the maximum administrable dose.. The current study was
initiated to assess the safety and dosing of Bel in patients with relapsed or
refractory Hodgkin and non-Hodgkin Lymphoma. Methods: 3-6 pts per dose cohort
were enrolled on study, at the following doses: A 750; B 1000; C 1250; D1500;E
1750; F 2000mg/d. Pts who met eligibility criteria (ANC = ; plts = ) with
evaluable disease were eligible. Definition of dose limiting toxicity (DLT)
included: related non-hem grade (gr) 3/4 tox; gr 4 neutropenia > 5 d or with
fever > 100.5 °F; gr 4 thrombocytopenia > 7 d.
Results: 28 pts, median age 48 (range 21-82),prior regimens: median 5,5 (range
0-13) , (17 had BM transplants, including 5 pts with allogeneic) have been
enrolled. Diagnoses include: HD (12 pts), mantle cell lymphoma (MCL;5 pts),
other NHL (11 pts). Most frequent adverse events seen in > 50% of patients
(regardless of attribution or gr) in 28 pts fully evaluable for toxicity:
diarrhea (25 pts), anorexia/decreased appetite (24 pts), fatigue (23 pts),
nausea (18 pts), vomiting (18 pts), cough (17 pts) and fever (15 pts). Non-hem
gr 3 events included diarrhea in 9 pts (evenly distributed over the co-horts),
grade 3 diarrhea at 1500 and 2000 mg dose were among the 4 DLT's . 5 pts with
gr 3/4 thrombocytopenia (shift from baseline) were seen in cohort C, D, E. 16
pts are evaluable to date, and include r, 1 CR (duration: 2+cycles)in NHL
patient, 1 PR (duration: 8 cycles) in HD patient, and stable disease have been
noted in 12 patients (duration: 1-24 cycles, median 1,5). Aside from the 1 CR
and 1 PR, tumor shrinkage between 25- 50% was noted in 8 pts.
Conclusions: Oral Bel can be delivered safely with a d 1-14, q3w schedule in
pts with lymphoma at a daily dose higher than what has been established for pts
with solid tumors. MTD for lymphoma pts was established at 1500 mg/d 1-14, q3w.
The safety profile and early tumor shrinkage noted in both HD, MCL and other
NHL warrants continued evaluation of Bel, especially in combination with other
active compounds.


Abstract 2598: Session: 615. Acute Myeloid Leukemia - Therapy, excluding
Transplantation: Poster II, Sunday, December 11, 2011, 6:00 PM-8:00 PM, Hall GH
(San Diego Convention Center)


Phase I Trial of Belinostat and Bortezomib in Patients with Relapsed or
Refractory Acute Leukemia, Myelodysplastic Syndrome, or Chronic Myelogenous
Leukemia in Blast Crisis


Beata Holkova, MD1, Mary Beth Tombes, RN1*, Ellen Shrader1*, Sheryl S. Cooke,
RN2*, Wen Wan, PhD1*, Heidi Sankala, PhD1*, Maciej Kmieciak, PhD1*, John D.
Roberts, MD1, Guillermo Garcia-Manero2 and Steven Grant, MD1

1Virginia Commonwealth University, Massey Cancer Center, Richmond, VA
2University of Texas, MD Anderson Cancer Center, Houston, TX


Numerous preclinical studies have demonstrated synergistic interactions between
proteasome and histone deacetylase (HDAC) inhibitors, particularly in B-cell
malignancies (e.g., myeloma and lymphoma). However, investigation of this
strategy in acute leukemias has been limited. Very recent preclinical findings
have shown marked synergism between the HDAC inhibitor belinostat and the
proteasome inhibitor bortezomib administered at very low (sub-micromolar)
concentrations, in various cultured and primary acute myelogenous leukemia and
acute lymphocytic leukemia specimens (Dai Y et al. Br J Haematol. 2011). These
interactions were associated with multiple perturbations in survival signaling
proteins, including inactivation of NF-kappa B, down-regulation of Bcl-xL and
XIAP, and up-regulation of the pro-apoptotic protein Bim. These findings
prompted initiation of a phase I trial with the primary objective of
determining the recommended phase II doses (RPTDs) for the combination of
bortezomib and belinostat in patients with relapsed or refractory acute
leukemia, myelodysplastic syndrome (MDS), or chronic myelogenous leukemia in
blast crisis (CML-BC).

To date, 13 patients have been enrolled. Patients with the following disease
types have been treated: acute leukemia (n=9), MDS (n=3), and CML-BC (n=1).
Patient characteristics include male/female ratio n = 6 (46%)/7 (54%), with a
median age of 59 years [range 27‑75]. ECOG performance score 0-2. The median
number of prior therapies was 2 [range 2-5]. The schedule of administration was
belinostat 30 minutes intravenous (IV) infusion on days 1-5 and 8-12; and
bortezomib IV bolus preceding belinostat on days 1, 4, 8, 11; on a 21 day
cycle. Dose level enrollment was: Level 1 = bortezomib 1.0 mg/m2, belinostat
500 mg/m2 (n=6); Level 2 = bortezomib 1.3 mg/m2, belinostat 500 mg/m2 (n=6);
and Level 3 = bortezomib 1.3 mg/m2, belinostat 650 mg/m2 (n=1). The study is
currently enrolling to dose level 3.

No dose-limiting toxicities (DLTs) have been observed to date. Non-DLTs (CTCAE
v4) include: leukopenia (grade 4, 23%), thrombocytopenia (grade 3, 15%), and
peripheral sensory neuropathy (grade 2, 23%). No serious adverse events have
occurred at unexpected frequency or severity. Two deaths have occurred due to
disease progression.

Of the 13 patients treated, 12 have been evaluable for response. There has been
1 complete response in this heavily pretreated population. This response was
achieved in a patient with biphenotypic acute leukemia, refractory to 7+3 and
Flag-Ida. The patient proceeded to allogeneic hematopoietic stem cell
transplantation. Four patients had stable disease, and 7 patients had
progressive disease. Correlative studies examining leukemic blast expression of
nuclear RelA, Bim, Bcl-xL, and XIAP pre- and post-treatment are ongoing.

Collectively, these findings indicate that a regimen combining belinostat and
bortezomib is well tolerated in patients with relapsed or refractory acute
leukemia, MDS, or CML-BC. The maximum tolerated dose (MTD) has not been
reached. Pending identification of the RPTDs, phase II evaluation of this
therapeutic strategy, if warranted, should define its activity more
definitively.


Præ-kliniske resuméer

Yderligere to præ-kliniske resuméer vil ligeledes blive præsenteret: Marci et
al, abstract number 2727, Amengual et al, abstract 3733 begge I forbindelse med
poster session 11, søndag den 11. december, 18.00-20.00.


Topotarget A/S


For yderligere information kontakt venligst:

Francois Martelet, CEO: Direkte: +45 39 17 83 41

Axel Mescheder, CMDO: Direkte: +45 39 17 83 14

Annette Lykke, IR Direkte: +45 39 17 83 44


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

Denne meddelelse kan indeholde fremadrettede udsagn, herunder udsagn om vores
forventninger til udviklingen af vores prækliniske og kliniske pipeline med
tidspunkter for igangsættelse og færdiggørelse af kliniske undersøgelser samt
med hensyn til forventet likviditetsforbrug. Sådanne udsagn er baseret på
ledelsens nuværende forventninger og er forbundet med risici og usikkerhed, som
kan medføre, at Topotargets faktiske resultater afviger væsentligt fra de
resultater, der beskrives i de fremadrettede udsagn. Topotarget advarer sine
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
faktorer, herunder, men ikke begrænset til, følgende: Risikoen for, at et eller
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. 20-11 Belinostat resumeer på ASH 2011.pdf