Topotargets meets primary endpoint!

Geil, Kursvervielfacher:

Belinostat pivotal BELIEF trial meets primary endpoint

To NASDAQ OMX Copenhagen A/S
Announcement no. 16-12 / Copenhagen, Denmark
September 21, 2012

Topotarget A/S today announced that the primary endpoint has been met for the belinostat pivotal trial for patients with peripheral T-cell lymphoma (PTCL).

The pivotal BELIEF trial (PXD101-CLN-19) evaluating the efficacy and safety of belinostat for the treatment of patients with relapsed/refractory PTCL met its primary endpoint. A Special Protocol Assessment (SPA) agreement with the U.S. Food and Drug Administration (FDA) requires the BELIEF trial to reach an objective response rate (ORR) of at least 20% and this objective was met. Data from the trial are being further analyzed and are expected to be communicated during Q4 2012.

Under the terms of a 2010 license and collaboration agreement, belinostat is currently being developed jointly by Spectrum Pharmaceuticals and Topotarget. Spectrum possesses the commercial rights to market belinostat in North America and India. A New Drug Application (NDA) for belinostat in PTCL is expected to be filed with the FDA by Spectrum in H1 2013.

Should Spectrum receive FDA’s acceptance to file the belinostat NDA, Topotarget is entitled to receive one million shares of common stock in Spectrum and a double-digit million USD cash payment. If belinostat is approved by the FDA, Topotarget will further receive a double-digit million USD cash payment.

BELIEF is a pivotal, open-label, multi-center, single-arm efficacy and safety trial of i.v. belinostat in patients with relapsed or refractory PTCL. FDA has granted belinostat Orphan Drug and Fast Track designation for the treatment of PTCL. The trial was initiated in December 2008 and recruitment was completed with 129 patients in September 2011. In total, the study included approximately 100 clinical centers globally.

PTCL is a hematological disease including a heterogeneous group of malignancies of T-cell origin that represents approximately 10-15% of all cases of non-Hodgkin’s lymphoma. PTCL is an aggressive, high-grade type of cancer with a poor prognosis of expected average survival of approximately two years from diagnosis without treatment. The projections for annual cancer incidences point to 15,500 new cases of PTCL in the US, Japan, and five largest EU countries.

Belinostat is a novel pan-HDAC inhibitor in late-stage clinical development with more than 1,000 patients treated. Belinostat has a promising safety profile, which allows combination with traditional chemotherapy. Preclinical experiments demonstrated belinostat to be effective against multiple cancers by inhibiting cell proliferation and inducing programed cell death (apoptosis) in tumor cells. Belinostat has been tested in a number of phase I/II clinical trials in hematological cancers and solid tumors both in mono- and combination therapy. Data from these trials have provided evidence of the anti-tumor effect of belinostat, including as monotherapy in PTCL and cutaneous T-cell lymphoma (CTCL), liver cancer, and thymoma.



Topotarget A/S  

EU Exclusivität nach meets primary endpoints, means multibagger for me:



Topotarget
Company Announcement

Belinostat gets EU Orphan Drug Designation for the treatment of peripheral T-cell lymphoma

To NASDAQ OMX Copenhagen A/S
Announcement no. 18-12 / Copenhagen, October 15, 2012

On October 15, 2012, the European Commission granted Topotarget A/S an Orphan Drug Designation for belinostat, its novel histone deacetylase (HDAC) inhibitor, for the treatment of peripheral T-cell lymphoma (PTCL). PTCL is a rare form of non-Hodgkin’s lymphoma.

“Obtaining Orphan Drug Designation for belinostat in PTCL in the European Union is an important milestone on the path to filing a registration dossier of belinostat in this region. This is positive news for Topotarget and potentially likewise for the rare disease patients with PTCL in need of new treatment options”, said Anders Fink Vadsholt, CEO of Topotarget.

Orphan Drug Designation
The EU regulation on orphan medicinal products is intended to encourage the development of drugs that may provide a significant benefit to patients suffering from rare (affecting fewer than five out of 10,000 people) and life-threatening or chronic debilitating conditions for which there is no effective therapies available. The orphan drug designation offers important incentives such as free protocol assistance (to optimize drug development) at the European Medicines Agency, fee reductions for various regulatory activities and following drug approval, and a grant of 10 years’ market exclusivity in the EU.

Belinostat was in September 2009 granted Orphan Drug Designation in the US by the U.S. Food and Drug Administration (FDA) for the treatment of PTCL.

Belinostat has clinical effect in the treatment of PTCL
Topotarget has recently announced that the primary efficacy endpoint for the belinostat pivotal BELIEF trial for patients with PTCL has been met in accordance with the Special Protocol Assessment with the FDA which requires the BELIEF trial to reach an objective response rate of at least 20%.

BELIEF is a pivotal, open-label, multi-center, single-arm efficacy and safety trial of i.v. belinostat in patients with relapsed or refractory PTCL. Data from the trial are being further analyzed and are expected to be communicated during Q4 2012. The trial was initiated in December 2008 and recruitment was completed with 129 patients in September 2011.

About belinostat
Belinostat is a novel pan-HDAC inhibitor in late-stage clinical development with more than 1,000 patients treated. Belinostat has a promising safety profile, which allows combination with traditional chemotherapy. Preclinical experiments demonstrated belinostat to be effective against multiple cancers by inhibiting cell proliferation and inducing programed cell death (apoptosis) in tumor cells. Belinostat has been tested in a number of phase I/II clinical trials in hematological cancers and solid tumors both in mono- and combination therapy. Data from these trials have provided evidence of the anti-tumor effect of belinostat, including as monotherapy in PTCL and cutaneous T-cell lymphoma (CTCL), liver cancer, and combination therapy in soft tissue sarcoma, ovarian cancer, and thymoma.

About PTCL
PTCL is a hematological disease including a heterogeneous group of malignancies of T-cell origin that represents approximately 10-15% of all cases of non-Hodgkin's lymphoma. PTCL is an aggressive, high-grade type of cancer with a poor prognosis of expected average survival of approximately two years from diagnosis without treatment. The projections for annual cancer incidences point to 15,500 new cases of PTCL in the US, Japan, and five largest EU countries.

Outlook for the year
This announcement does not change the previously announced outlook statement published on August 29, 2012.



Topotarget A/S

For further information, please contact:

Anders Vadsholt, CEO: Direct: +45 39 17 83 45; Cell: +45 28 98 90 55

Axel Mescheder, CMDO: Direct: +45 39 17 83 14; Cell: +45 51 55 71 66

Background information

About Topotarget
Topotarget (NASDAQ OMX: TOPO) is an international biopharmaceutical company headquartered in Copenhagen, Denmark, dedicated to clinical development and registration of oncology products. In collaboration with Spectrum Pharmaceuticals, Inc., Topotarget focuses on the development of its lead drug candidate, belinostat, which has shown positive results in the treatment of  hematological malignancies and solid tumors, obtained by both mono- and combination therapy. For more information, please refer to www.topotarget.com.

Topotarget Safe Harbor Statement
This announcement may contain forward-looking statements, including statements about our expectations of the progression of our preclinical and clinical pipeline including the timing for commencement and completion of clinical trials and with respect to cash burn guidance. Such statements are based on management's current expectations and are subject to a number of risks and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. Topotarget cautions investors that there can be no assurance that actual results or business conditions will not differ materially from those projected or suggested in such forward-looking statements as a result of various factors, including, but not limited to, the following: The risk that any one or more of the drug development programs of Topotarget will not proceed as planned for technical, scientific, or commercial reasons or due to patient enrollment issues or based on new information from non-clinical or clinical studies or from other sources; the success of competing products and technologies; technological uncertainty and product development risks;  uncertainty of additional funding; Topotarget's history of incurring losses and the uncertainty of achieving profitability; Topotarget's stage of development as a biopharmaceutical company; government regulation; patent infringement claims against Topotarget's products, processes, and technologies; the ability to protect Topotarget's patents and proprietary rights; uncertainties relating to commercialization rights; and product liability exposure. We disclaim any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events, or otherwise, unless required by law.

Attachments:
Announcement no. 18-12 Belinostat gets EU Orphan Drug Designation for treatm  

TopoTarget
Unternehmensmitteilung

Belinostat hat günstige Sicherheitsprofil bei PTCL BELIEF Studie

Um NASDAQ OMX Copenhagen A / S
Bekanntmachung Nr. 01-13 / Kopenhagen, 24. Januar 2013

TopoTarget A / S (NASDAQ OMX: TOPO) gibt bekannt, dass klinische Daten Belinostat werden an der 5 dargestellt th Annual T-Zell-Lymphom Forum on January 24-26, 2013, San Francisco, USA.

Die abstrakte enthält die vorläufigen Sicherheitsdaten aus der Phase-II-Studie BELIEF (CLN-19) von Belinostat als Monotherapie bei Patienten mit rezidivierten und / oder refraktären peripheren T-Zell-Lymphom (PTCL). wird der Schluss gezogen, dass Belinostat gut ist toleriert mit einem günstigen Sicherheitsprofil bei Patienten mit PTCL und dass Belinostat ist ein Kandidat für eine gut verträgliche Alternative zur Behandlung dieser Krankheit. Das Plakat geplant ist auf der Konferenz 26. Januar 2013 vorgestellt werden.

Die abstrakten Text ist nachfolgend dargestellt:

Belinostat in rezidivierten und / oder refraktären peripheren T-Zell-Lymphom (R / R PTCL): Vorläufige Ergebnisse zur Sicherheit

Autoren: Owen O'Connor, Steve Horwitz, Tamas Masazi, Lauren Pinter-Brown, Shanta Chawla, Andrei Shustov

Hintergrund: Die Prognose für Patienten mit R / R PTCL bleibt arm. Romidepsin und Pralatrexat sind in den USA zugelassen, mit insgesamt Ansprechraten (ORR) von 25% bzw. 27% 1, 2 . Pralatrexat, ein Anti Folsäure, verursacht Myelosuppression und Mukositis. Müdigkeit war prominent mit Romidepsin ein HDACi. Diese Klasse wurde in QTc-Verlängerung in Verbindung gebracht. Belinostat, ein Roman pan-HDAC, in der Voruntersuchung hat ähnliche ORR in R / R PTCL und ist gut mit gemeinsamen Grad 1-2 Toxizitäten, Magen-Darm-und verfassungsrechtlichen toleriert 3 . Diese Befunde waren nicht gedämpft in Kombination Studien 4 . Glaube ist die entscheidende Ph-2-Studie, die die Sicherheit und Wirksamkeit von Belinostat in R / R PTCL ausgewertet. Wir präsentieren die vorläufigen Daten zur Sicherheit aus dem Glauben Studie.

Methoden: Der Glaube ist eine offene, multizentrische, einarmige Wirksamkeit und Sicherheit Studie bei Patienten mit R / R PTCL nach Versagen von mindestens einer systemischen Therapie. PTCL Diagnose wurde durch die zentrale Pathologie Berichtsjahr bestätigt. EKGs wurden zentral überprüft. Wichtige Einschlusskriterien waren: Thrombozytenzahl ≥ 50.000 / ul, keine vorherige HDACi Therapie, messbarer Erkrankung und angemessene Organfunktion. Belinostat wurde als 30 min IV-Infusion bei 1000 gegebenen mg / m 2 an den Tagen 1-5 der 3-wöchigen Zyklus bis Fortschreiten der Krankheit oder unannehmbare Toxizität. Der primäre Endpunkt war ORR. Die Sicherheit wurde durch 30 Tage der letzten Dosis von Belinostat überwacht. Wirksamkeit Bestimmungen sind im Gange.

Ergebnisse: Insgesamt 129 Patienten, 53% Männer, Durchschnittsalter 63 Jahre (Bereich 29-81 Jahre) behandelt wurden. Die mittlere Zahl der Zyklen war 2 (Bereich 1-31). Eine Dosisreduktion trat bei 11% der Patienten und 1% hatten zwei Dosisreduktion. AEs führte Dosis Verzögerungen bei 21% der Patienten und 18% für AES eingestellt, einschließlich Tod. Grad 3/4 nicht hämatologische Nebenwirkungen beobachtet in> 3% der Patienten enthalten Asthenie / Müdigkeit 9%, Lungenentzündung 7%, Dyspnoe 6%, Infektion 4%, fiebrige Neutropenie 4%, Pruritus 3%, tiefe Venenthrombose 3% und Hypotonie 3%. Grade 3 QTc-Verlängerung wurde in 2% der Patienten berichtet. Grad 3/4 hämatologischen Toxizitäten waren: Thrombozytopenie 6% bei Patienten mit einer Thrombozytenzahl von ≥ 100.000, Anämie, Leukopenie und Neutropenie jeweils 13%. Insgesamt 23 Patienten (18%) starben bei der Behandlung oder innerhalb von 30 Tagen nach der letzten Dosis, vorwiegend aufgrund von PTCL Progression. Kein Tod wurde Belinostat zugeschrieben.

Schlussfolgerungen: Belinostat ist gut mit einem günstigen Sicherheitsprofil bei Patienten mit R / R PTCL toleriert. Basierend auf Wirksamkeit in der früheren Ph-2-Studie und die Sicherheit in dem Glauben Studie ist Belinostat eine mutmaßliche gut verträgliche Option für die Behandlung von PTCL. Andere Studien zeigen, dass die volle Dosen Belinostat mit anderen zytotoxischen Therapien machen Kombinationstherapie für Patienten mit PTCL machbar kombiniert werden können.

TopoTarget A / S

Für weitere Informationen kontaktieren Sie bitte:

Anders Vadsholt, CEO: Direkt: +45 39178345

Hintergrundinformationen

Über TopoTarget
TopoTarget (NASDAQ OMX: TOPO) ist ein internationales biopharmazeutisches Unternehmen, das in Kopenhagen, Dänemark, die sich mit der klinischen Entwicklung und Registrierung von onkologischen Produkten. In Zusammenarbeit mit Spectrum Pharmaceuticals, Inc., konzentriert sich TopoTarget auf die Entwicklung seines führenden Medikamentenkandidaten, Belinostat, die positive Ergebnisse bei der Behandlung von hämatologischen Malignomen und soliden Tumoren, sowohl Mono-und Kombinationstherapie erhalten gezeigt hat. Für weitere Informationen, lesen Sie bitte www.topotarget.com.

Über Belinostat
Belinostat ist ein neuartiges pan-HDAC-Inhibitor in der späten Phase der klinischen Entwicklung mit mehr als 1.000 Patienten behandelt. Belinostat hat eine vielversprechende Sicherheitsprofil der Kombination ermöglicht mit traditionellen Chemotherapie. Präklinische Experimente zeigten Belinostat wirksam gegen verschiedene Krebsarten durch die Hemmung der Zellproliferation und induziert programmierten Zelltod (Apoptose) in Tumorzellen. Belinostat hat in einer Reihe von Phase I / II-Studien bei hämatologischen Krebserkrankungen und soliden Tumoren sowohl in Mono-und Kombinationstherapie getestet. Daten aus diesen Studien haben Beweise für die Anti-Tumor-Wirkung von Belinostat, auch als Monotherapie bei PTCL und kutane T-Zell-Lymphom (CTCL), Leberkrebs und Thymom vorgesehen.

Über den Glauben Studie
Glaube ist ein zentraler, open-label, multizentrische, einarmige Wirksamkeit und Sicherheit Studie von iv Belinostat bei Patienten mit rezidivierten oder refraktären PTCL. FDA hat Belinostat Orphan Drug and Fast Track Designation zur Behandlung von PTCL gewährt. Die Studie wurde im Dezember 2008 begonnen und die Rekrutierung wurde mit 129 Patienten im September 2011 abgeschlossen. Insgesamt umfasste die Studie ca. 100 klinischen Zentren weltweit.

TopoTarget Safe Harbor Statement
Diese Mitteilung enthält zukunftsgerichtete Aussagen, einschließlich Aussagen über TopoTarget A / S 'Erwartungen an das Fortschreiten der TopoTarget A / S' klinische Pipeline und in Bezug auf Cash-Burn Führung. Solche Aussagen unterliegen Risiken und Unsicherheiten, von denen viele außerhalb der Kontrolle von TopoTarget A / S, und dass sich die tatsächlichen Ergebnisse erheblich von jenen unterscheiden, beschrieben. TopoTarget A / S lehnt jegliche Absicht oder Verpflichtung zur Aktualisierung oder Überprüfung zukunftsgerichteter Aussagen, gleich ob als Ergebnis neuer Informationen, zukünftiger Ereignisse oder aus sonstigen Gründen, ausgenommen nach dänischem Recht erforderlich.

Anhänge:
Announcement Nr. 01-13 Belinostat hat günstige Sicherheitsprofil bei PTCL BELIEF study.pdf  

Belinostat BELIEF trial exceeds primary endpoint with encouraging response rate

To NASDAQ OMX Copenhagen A/S
Announcement no. 03-13 / Copenhagen, March 5, 2013

Final top-line data confirm that the primary endpoint was met for the belinostat pivotal trial for patients with relapsed or refractory peripheral T-cell lymphoma (PTCL) with an encouraging objective response rate.

Top-line data show an objective response rate (ORR) in the efficacy analysis set which is above the protocol criterion for a positive outcome of the trial. Belinostat thus has an ORR that is on par with the accelerated approved drugs Folotyn™ and Istodax®. A Special Protocol Assessment agreement with the US Food and Drug Administration (FDA) required the CLN-19 BELIEF trial to reach an ORR of at least 20%. The FDA has granted belinostat Orphan Drug and Fast Track designation for the treatment of PTCL. All patients who received at least one dose of belinostat and had a confirmed PTCL diagnosis by the central pathology review were included in the efficacy analysis set. The responses have been confirmed by central independent radiology review. Final data have been submitted for presentation to the 2013 ASCO annual meeting.

“Our belief in belinostat has never wavered and the encouraging objective response rate together with the earlier announced favorable safety profile further supports the potential of our product. We strive to improve the lives of cancer patients and this is a large step in the right direction" said Anders Vadsholt, CEO of Topotarget.

Favorable safety profile
On January 24, 2013, Topotarget announced that preliminary safety data from the BELIEF trial in PTCL, presented at the T-Cell Lymphoma Forum 2013 in San Francisco, USA, showed that belinostat has a favorable safety profile and that the compound has the potential to become a well-tolerated alternative for the treatment of PTCL. The favorable safety outcome from this trial, as well as experience from earlier belinostat trials, shows that full doses of belinostat can be combined with other cytotoxic regimens making combination therapy for cancer patients feasible. The low incidence of myelosuppression is of special notice as this offers the opportunity to combine belinostat with other cytostatic agents for the treatment of patients with PTCL.

New Drug Application
Belinostat is currently being developed jointly by Topotarget and Spectrum Pharmaceuticals. Spectrum possesses the commercial rights to market belinostat in North America and India. A New Drug Application (NDA) for belinostat in PTCL is expected to be filed with the FDA by Spectrum in mid-2013.

 

Conference call

A conference call will be held today, March 5, 2013, at 1:00 pm CET.

CEO Anders Vadsholt will make a presentation of the BELIEF study and answer questions. The teleconference will be conducted in English. A presentation will be available on Topotarget’s website, www.topotarget.com, before the start of the conference call.

To participate in the conference call please dial:

Denmark: 32 72 80 18
International: +44 (0) 1452 555131
USA: 18666828490
Conference ID: 19438536

You will be able to stream the telephone conference via the following link:  

Company Announcement

Positive subtype data from the BELIEF trial presented at the 12th International Conference on Malignant Lymphoma

To NASDAQ OMX Copenhagen A/S

Announcement no. 18-13 / Copenhagen, June 17, 2013

Topotarget announces that positive subtype data on angioimmunoblastic T-cell lymphoma (AITL) from the BELIEF trial with belinostat in relapsed or refractory peripheral T-cell lymphoma (R/R PTCL) will be presented at the 12th International Conference on Malignant Lymphoma (ICML) in Lugano, Switzerland, on June 19-22, 2013.

The belinostat abstract, which will be presented orally at the ICML conference, puts special emphasis to the BELIEF trial’s subtype AITL, which has shown an objective response rate (ORR) of 45.5%. The abstract further concludes that the favorable safety profile observed warrants further investigation of belinostat-based regimens to optimize outcomes for AITL.

“The PTCL subtype, AITL, represents 15-20% of all PTCL cases and we are hence very thrilled that belinostat shows a response rate of an astounding 45.5%, which places our compound at the top of available treatments in the indication”, says Anders Vadsholt, CEO of Topotarget A/S.

Below is the full-length abstract, which will be presented on June 22, 2013.

Belinostat in relapsed or refractory peripheral T-cell lymphoma (R/R PTCL) subtype angioimmunoblastic T-cell lymphoma (AITL): Results from the pivotal BELIEF trial.

S. Horwitz; O. O’Connor, W. Jurczak; A.Van Hoof; G. Hess; Z. Gasztonyl; J.K. Doorduijn; J. Walewski; P. Brown; A.Vranovsky; Sissolak; I. Auer; A. Duletic-Nacinovic; A. Shustov; S. Chawla; P. Knoblauch; G. Wulf; O. Visser; P. L. Zinzani;  T. Masszi.

Introduction: PTCL is a heterogeneous, aggressive disease with poor prognosis. AITL is a subtype representing 15–20% of PTCL. AITL treatment is similar to other forms of PTCL with 5-year OS rates of 10–32%.

Methods: BELIEF was a single-arm study of belinostat in patients with R/R PTCL after failure of ≥1 prior systemic therapies. Entry criteria were measurable disease, platelets≥50,000/ml, no prior histone deacetylase inhibitor (HDACi) therapy, and adequate organ function. PTCL was confirmed by central pathology review group (CPRG). Belinostat (1000mg/m, 2 IV_5 days) was given as a 3week cycle until progression or unacceptable toxicity. Tumor response was assessed by Cheson 2007 criteria. The primary endpoint was ORR. Subgroup analysis examined response by PTCL subtype.

Results: Of 129 patients enrolled with R/R PTCL, data presented here are from22 patients with CRPG confirmed AITL, including 5 with baseline platelets <100,000/ml, a median age of 70 (range 48–78) years, 64% female, a median of 2 (range 1–5) prior therapies (21 CHOP/CHOP-like; 4 stem cell transplant), and 8 had bone marrow involvement. Belinostat was administered for a median of 4 cycles (1–29) with a median dose intensity of 94%. Dose reductions in 3 patients were due to grade 2 and 3 QTC prolongation in 1 patient, immune hemolytic anaemia, and hypokalemia/dyspnea/fever. Response rate for AITL was 45% (4 CR, 6 PR) with a median duration of response of 7.5 (1.6–29.4) months. Of the responders, 2 had baseline platelets of 78,000 and 79,000; with one patient achieving CR. Data is reported as of 31AUG2012, with 3 patients remaining on treatment at 55, 105, and 135 weeks* and 19 discontinued. Discontinuations were due to PD in 14 patients, AEs in 2 and other reasons for 3. Sixteen patients have died, 5 were alive, and 1was lost to follow-up. Median PFS and OS for patients with AITL were 5.8 and 9.2 mos, respectively.

Conclusions: Belinostat treatment resulted in a 45% response rate among patients with R/R AITL. The favorable safety profile observed warrants further investigation of belinostat-based regimens to optimize outcomes for AITL.

*Please note that there is a typo in the abstract made public on http://onlinelibrary.wiley.com/doi/10.1002/hon.2057/abstract; months should read weeks.


Topotarget A/S

For further information, please contact:

Anders Vadsholt, CEO: Direct: +45 39178345

Background information

About Topotarget

Topotarget (NASDAQ OMX: TOPO) is a Scandinavian-based biopharmaceutical company headquartered in Copenhagen, Denmark, dedicated to clinical development and registration of oncology products. In collaboration with Spectrum Pharmaceuticals, Inc., Topotarget focuses on the development of its lead drug candidate, belinostat, which has shown positive results in the treatment of hematological malignancies and solid tumors, obtained by both mono- and combination therapy. For more information, please refer to www.topotarget.com.

Topotarget Safe Harbor Statement

This announcement may contain forward-looking statements, including statements about Topotarget A/S’ expectations to the progression of Topotarget A/S’ clinical pipeline and with respect to cash burn guidance. Such statements are subject to risks and uncertainties of which many are outside the control of Topotarget A/S, and which could cause actual results to differ materially from those described. Topotarget A/S disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events, or otherwise, unless required by Danish law.