BRANFORD, Conn., Aug. 10 /PRNewswire-FirstCall/ -- CuraGen Corporation and TopoTarget A/S (Copenhagen Stock Exchange: TOPO) announced today the initiation of a Phase I clinical trial evaluating the administration of oral PXD101, a small molecule histone deacetylase (HDAC) inhibitor, in patients with advanced solid tumors. The Phase I trial will be led by Dr. W. Kevin Kelly, Associate Professor of Medicine in the Section of Medical Oncology and head of The Prostate & Urologic Oncology Program at the Yale Cancer Center, New Haven, CT.
The Phase I study is an open-label, multi-center trial designed to establish the maximum tolerated dose (MTD) for oral PXD101 administered once or twice daily. Patients will be treated with oral PXD101 in a dose-escalation regimen and may continue to receive up to eight or more treatment cycles depending on disease response. Primary objectives for the study include evaluation of the safety, tolerability and pharmacokinetics of oral PXD101. Secondary objectives include assessment of the pharmacokinetic profile of oral PXD101 administered once or twice daily at various dose levels and evaluation of anti-tumor activity. The study is being conducted at sites both in the United States and Europe, with preliminary results expected to be available by the end of 2007.
"We believe that the availability of both an oral and intravenous (IV) dosage form of PXD101 will confer a strategic advantage to our HDAC inhibitor development program," commented Dr. Frank Armstrong, President and Chief Executive Officer of CuraGen. "IV PXD101 may be preferable in mono- or combination therapy against aggressive cancers, while the use of oral PXD101 may be preferable for maintenance or chronic treatment of relatively more indolent diseases such as bladder, prostate or thyroid cancers.
In a previously conducted pilot clinical study, oral PXD101 was demonstrated to achieve significant plasma concentrations and have an oral bioavailability of approximately 33% (Poster C88, AACR-NCI-EORTC International Conference, Molecular Targets and Cancer Therapeutics). These data, in part, support the continued evaluation of PXD101 in this comprehensive Phase I trial.
CuraGen and TopoTarget continue to evaluate IV PXD101 in a number of Phase II trials including PXD101 monotherapy in patients with multiple myeloma (MM), T-cell lymphomas, and acute myelogenous leukemia. In addition, multiple Phase Ib/II clinical trials are being conducted to evaluate the combination of PXD101 with 5-fluorouracil for colorectal cancer, with carboplatin and paclitaxel for ovarian cancer, with cis-retinoic acid for advanced solid tumors, and with Velcade(R) (bortezomib) for Injection for MM.
About PXD101
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. PXD101 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 and Velcade(R) (bortezomib) for Injection.
Intravenously administered PXD101 is currently being evaluated in multiple clinical trials as a potential treatment for multiple myeloma, T-cell lymphomas, acute myelogenous leukemia, mesothelioma and colorectal and ovarian cancers, either alone or in combination with anti-cancer therapies. In August 2004, CuraGen signed a Clinical Trials Agreement with the NCI under which the NCI will sponsor several clinical trials to investigate PXD101 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 pre-clinical and non-clinical studies on PXD101 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, including novel protein, antibody, and small molecule therapeutics, that aim to offer hope for patients with cancer, inflammatory diseases, and diabetes. CuraGen's strategic alliances have resulted in a deep pipeline of potential therapeutics that is being developed by the Company's experienced research and development teams. By leveraging the drug development strengths cultivated over the years, CuraGen expects to make a difference in the lives of patients by bringing forward promising therapeutics that address unmet medical needs. To further capitalize on CuraGen's extensive research and development expertise, CuraGen founded a majority-owned subsidiary, 454 Life Sciences, which has developed and is commercializing advanced technologies for the sequencing of DNA. CuraGen and 454 Life Sciences are headquartered in Branford, Connecticut. For additional information on the companies please visit http://www.curagen.com and http://www.454lifesciences.com.
About TopoTarget
TopoTarget (CSE: TOPO) is a biopharmaceutical company, headquartered in Denmark and with subsidiaries in the UK and Germany, 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 eight drugs are in clinical development, of both novel anti-cancer therapeutics and new cancer indications for existing drugs. The most advanced drug candidate, Savene(TM) for extravasations is expected on the market end 2006. 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
This press release contains forward-looking statements including statements about the expected effects and benefits of PXD101. We caution 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 PXD101 or any other CuraGen drug development program 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; technological uncertainty and product development risks; uncertainty of additional funding; CuraGen's history of incurring losses and the uncertainty of achieving profitability; CuraGen's stage of development as a biopharmaceutical company; government regulation; patent infringement claims against CuraGen's products, processes and technologies; the ability to protect CuraGen's patents and proprietary rights; uncertainties relating to commercialization rights; and product liability exposure. Please refer to CuraGen's Annual and Quarterly Reports on Forms 10-K and 10-Q for a complete description of these risks. CuraGen 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 law.
Velcade(R) (bortezomib) for Injection is a registered trademark of Millennium Pharmaceuticals, Inc.
Contact: CuraGen Corporation Glenn Schulman, Pharm.D. Assistant Director of Investor Relations gschulman@curagen.com (888) 436-6642
CuraGen CorporationCONTACT: Glenn Schulman, Pharm.D., Assistant Director of InvestorRelations at CuraGen Corporation, 1-888-436-6642, gschulman@curagen.com
