TopoTarget and CuraGen Initiate Phase I/II Clinical Trial of Belinostat (PXD101) Combination Therapy for Soft Tissue Sarcomas

TopoTarget A/S
Symbion
Fruebjergvej 3
DK 2100 Copenhagen
Denmark
Tel: +45 39 17 83 92
Fax: +45 39 17 94 92
CVR-nr: 25695771
www.topotarget.com

To the Copenhagen Stock Exchange
Announcement No. 15-07 / Copenhagen 1 May 2007


TopoTarget and CuraGen Initiate Phase I/II Clinical Trial of Belinostat (PXD101) Combination Therapy for Soft Tissue Sarcomas 


Copenhagen, Denmark - 1 May, 2007 - TopoTarget A/S (Copenhagen Stock Exchange: TOPO) and CuraGen Corporation (NASDAQ: CRGN) announced today the initiation of a Phase I/II open-label, multi-center clinical trial evaluating the efficacy and safety of intravenous belinostat (PXD101), an HDAC inhibitor, in combination with doxoru-bicin for the treatment of Soft Tissue Sarcomas (STS).  

The Phase I/II clinical trial is being led by MD, D.Msc, Head, Department of Oncology, Aarhus University Hospital, DK, Dr. Ole Steen Nielsen. Additional sites include the Royal Marsden Hospital in London and Herlev Hospital, DK. During the initial dose escalation part of the trial up to 24 patients with solid tumors for whom no standard therapy exists will be enrolled in order to de-fine the maximal tolerated dose (MTD) of belinostat in combination with doxorubicin. 

Upon determination of the MTD, the trial will advance into phase II and enrol additional 20-40 STS patients who have not received prior chemotherapy. Patients will receive their standard chemotherapy of doxorubicin every 3 weeks to which belinostat will be added in a 5-day intravenous regimen. Pa-tients demonstrating complete or partial response will continue to receive treatment with the combination for up to eight cycles or until disease pro-gression.

“Already in our cancer models we saw antitumor activity of belinostat in soft tissue sarcomas and also a synergistic effect when combined with doxorubi-cin. This and the first clinical results lead us to believe that belinostat could be a potential treatment of patients with soft tissue sarcoma.  There is a clear medical need for improved therapy and positive results from the trial would be very good news for this group of cancer patients”, says Peter Buhl Jensen, CEO of TopoTarget.

The primary objectives for the study are to determine the MTD, and to assess the antitumor activity of belinostat and doxorubicin combination treatment as defined by the commonly used RECIST criteria. Secondary objectives include the time to disease progression, overall survival, duration of response and toxicity. The pharmacokinetic profile and aspects of pharmacodynamic activ-ity of belinostat will also be evaluated. 

“Preliminary antitumor activity has been reported with belinostat in patients with soft tissue sarcomas in a phase I clinical trial. In this new clinical trial we plan to evaluate the safety of belinostat in combination with doxorubicin, a commonly used treatment for patients with soft tissue sarcoma, and hope to enhance its antitumor effect without causing significant increase in toxicity,” commented Dr. Ole Steen Nielsen, Aarhus University.

The initiation of this trial does not change TopoTarget's financial expectations for full-year 2007.

TopoTarget A/S

For further information, please contact:

Dr. Peter Buhl Jensen		 Telephone +45 39 17 83 41
Chief Executive Officer		 Mobile	  +45 21 60 89 22

Tim Corcoran			 Telephone +44 1235 443 713
Chief Operating Officer		 Mobile	  +44 787 656 1027

Background information

About Soft Tissue Sarcoma (STS)
Soft Tissue Sarcomas (STS) are rare tumors with an annual incidence around 2 to 3 per 100,000 with more than 9,000 cases expected to be diagnosed during 2007 in the U.S. Overall, STS account for approximately 1% of all malignancies. The 5-year survival in Europe of adult STS diagnosed at an early stage is nearly 90%, although the median survival for patients with metastatic disease is typically less than 1 year. 

Standard treatment for STS is generally a wide surgical excision of the primary tumor combined with adjuvant radiotherapy, whenever feasible. Surgery alone is followed by a high incidence of local recurrence, which is reduced by the addition of post-operative radiotherapy. However, even an optimal local treatment does not prevent the occur-rence of distant metastases.  Chemotherapy is widely used in the treatment of ad-vanced disease, but is so far mainly palliative.  Doxorubicin appears to be the most active drug in the treatment of STS and activity has been noted in pretreated patients. 

About belinostat (PXD101)
Belinostat is a promising small molecule HDAC inhibitor being investigated for its role in the treatment of a wide range of solid and hematologic malignancies either as a single-agent, or in combination with other active anti-cancer agents, including 5-fluorouracil (5-FU), carboplatin, paclitaxel, cis-retinoic acid, azacitidine, and Velcade® (bortezomib) for Injection.  HDAC inhibitors represent a new mechanistic class of anti-cancer thera-peutics that target HDAC enzymes and have been shown to: arrest growth of cancer cells (including drug resistant subtypes); induce apoptosis, or programmed cell death; promote differentiation; inhibit angiogenesis; and sensitize cancer cells to overcome drug resistance when used in combination with other anti-cancer agents.  

Intravenous belinostat is currently being evaluated in multiple clinical trials as a poten-tial treatment for multiple myeloma, T- and B-cell lymphomas, AML, mesothelioma, liver, colorectal and ovarian cancers, either alone or in combination with anti-cancer therapies.  An oral formulation of belinostat is also being evaluated in a Phase I clinical trial for patients with advanced solid tumors. In August 2004, CuraGen signed a Clinical Trials Agreement with the NCI under which the NCI will sponsor several clinical trials to investigate belinostat for the treatment of various cancers, both as a single-agent and in combination chemotherapy regimens.  In May 2005, TopoTarget announced the signing of a Cooperative Research and Development Agreement (CRADA) with the NCI to con-duct preclinical and nonclinical studies on belinostat in order to better understand its anti-tumor activity and to provide supporting information for clinical trials.

About TopoTarget
TopoTarget (OMX - The Nordic Exchange: TOPO) is a biopharmaceutical company, headquartered in Denmark and with subsidiaries in the UK, Germany and the USA, dedicated to finding ''Answers for Cancer'' and developing improved cancer therapies. TopoTarget is founded and run by clinical cancer specialists and combines years of hands-on clinical experience with in-depth understanding of the molecular mechanisms of cancer. Focus lies on highly predictive cancer models and key cancer enzyme regula-tors (mainly HDAC, mTOR, and topoisomerase II inhibitors) and a strong development foundation has been built. TopoTarget has a broad portfolio of small molecule preclini-cal drug candidates and seven drugs are in clinical development, including both novel anti-cancer therapeutics and new cancer indications for existing drugs. Savene™ is TopoTarget's first product on the market. In addition to organic growth, TopoTarget consistently looks for opportunities to strengthen and expand its activities through acquisitions and in-licensing. For more information, please refer to Hwww.topotarget.com.H

About CuraGen
CuraGen Corporation (NASDAQ: CRGN) is a biopharmaceutical company developing diverse approaches, including novel protein, antibody, antibody-drug conjugate and small molecule therapeutics.  By leveraging the drug development strengths cultivated over the years, CuraGen expects to make a difference by advancing its promising therapeutics to address the unmet medical needs of patients with cancer and inflamma-tory diseases.  CuraGen is focused on bringing velafermin, belinostat and CR011-vcMMAE through clinical development, and maintains a portfolio of earlier-stage com-pounds that have the potential to treat cancer and inflammatory diseases.  CuraGen Corporation is headquartered in Branford, Connecticut.  For additional information please visit www.curagen.com.

TopoTarget Safe Harbour Statement
This announcement may contain forward-looking statements, including statements about our expectations of the progression of our preclinical and clinical pipeline includ-ing 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 enrolment issues or based on new information from nonclinical or clinical studies or from other sources; the success of competing products and technolo-gies; technological uncertainty and product development risks;  uncertainty of addi-tional 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 expo-sure; 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.