BRANFORD, Conn., May 2 /PRNewswire-FirstCall/ -- CuraGen Corporation and TopoTarget A/S (Copenhagen Stock Exchange: TOPO) 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 doxorubicin for the treatment of Soft Tissue Sarcomas (STS).
The Phase I/II clinical trial is being led by Ole Steen Nielsen, M.D., D.Msc., Head, Department of Oncology, Aarhus University Hospital, DK. 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 define the maximal tolerated dose (MTD) of belinostat in combination with doxorubicin.
Upon determination of the MTD, the trial will advance into Phase II and enroll an additional 20 to 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. Patients demonstrating complete or partial response will continue to receive treatment with the combination for up to eight cycles or until disease progression.
“The antitumor activity of belinostat we observed in preclinical models, combined with previously generated clinical results suggest there is activity of belinostat for the treatment of STS, and leads us to believe that the combination of belinostat and doxorubicin could benefit patients with this disease. There is a clear medical need for improved therapy and we look forward to evaluating the potential of this combination,” commented Frank Armstrong, M.D., President and Chief Executive Officer of CuraGen Corporation.
The primary objectives for the study are to determine the MTD, and to assess the anti-tumor activity of belinostat and doxorubicin combination treatment as defined by RECIST criteria. Secondary objectives include the time to disease progression, overall survival, and duration of response. The pharmacokinetic profile and aspects of pharmacodynamic activity 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.
About Soft Tissue Sarcoma
Soft Tissue Sarcomas (STS) are rare tumors with an annual incidence of 2 to 3 cases 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 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 occurrence of distant metastases. Chemotherapy is widely used in the treatment of advanced 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-FU, carboplatin, paclitaxel, cis-retinoic acid, azacitidine and Velcade(R) (bortezomib) for Injection. HDAC inhibitors represent a new mechanistic class of anti-cancer therapeutics 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 potential treatment for multiple myeloma, T- and B-cell lymphomas, AML, mesothelioma, liver, colorectal, 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 conduct preclinical and nonclinical studies on belinostat in order to better understand its anti-tumor activity and to provide supporting information for clinical trials.
About CuraGen
CuraGen Corporation is a biopharmaceutical company developing diverse approaches for treating cancer; 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 inflammatory diseases. CuraGen is focused on bringing velafermin, belinostat and CR011- vcMMAE through clinical development, and maintains a portfolio of earlier- stage compounds that have the potential to treat cancer and inflammatory diseases. CuraGen Corporation is headquartered in Branford, Connecticut. For additional information please visit http://www.curagen.com
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 regulators (mainly HDAC, mTOR, and topoisomerase II inhibitors) and a strong development foundation has been built. TopoTarget has a broad portfolio of small molecule preclinical drug candidates and seven drugs are in clinical development, including both novel anti-cancer therapeutics and new cancer indications for existing drugs. Savene(TM) 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 http://www.topotarget.com
Safe Harbor
Statements in this press release regarding management’s future expectations, beliefs, intentions, goals, strategies, plans or prospects, including statements relating to the expected benefits of belinostat and plans to characterize the pharmacokinetic and pharmacodynamic profile of belinostat in STS, may constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements can be identified by terminology such as “anticipate,” “believe,” “could,” “could increase the likelihood,” “estimate,” “expect,” “intend,” “is planned,” “may,” “should,” “will,” “will enable,” “would be expected,” “look forward,” “may provide,” “would” or similar terms, variations of such terms or the negative of those terms. Such forward-looking statements involve known and unknown risks, uncertainties and other factors including the risk that any one or more of CuraGen’s drug development programs will not proceed as planned for technical, scientific or commercial reasons or due to patient enrollment issues or based on new information from nonclinical or clinical studies or from other sources, the success of competing products and technologies, CuraGen’s stage of development as a biopharmaceutical company, government regulation and healthcare reform, technological uncertainty and product development risks, product liability exposure, uncertainty of additional funding, CuraGen’s history of incurring losses and the uncertainty of achieving profitability, reliance on research collaborations and strategic alliances, competition, patent infringement claims against CuraGen’s products, processes and technologies, CuraGen’s ability to protect its patents and proprietary rights and uncertainties relating to commercialization rights, as well as those risks, uncertainties and factors referred to in the Company’s Annual Report on Form 10-K for the year ended December 31, 2006, filed with the Securities and Exchange Commission under the section “Risk Factors,” as well as other documents that may be filed by CuraGen from time to time with the Securities and Exchange Commission. As a result of such risks, uncertainties and factors, the Company’s actual results may differ materially from any future results, performance or achievements discussed in or implied by the forward-looking statements contained herein. CuraGen is providing the information in this press release as of this date and assumes no obligations to update the information included in this press release or revise any forward-looking statements, whether as a result of new information, future events or otherwise.
Contact: Glenn Schulman, Pharm.D. Director of Investor Relations gschulman@curagen.com (888) 436-6642 CRGN-P
CuraGen Corporation
CONTACT: Glenn Schulman, Pharm.D., Director of Investor Relations ofCuraGen Corporation, +1-888-436-6642, gschulman@curagen.com
