BRANFORD, Conn., Nov. 14 /PRNewswire-FirstCall/ -- CuraGen Corporation and TopoTarget A/S (Copenhagen Stock Exchange: TOPO) announced today the initiation of patient dosing in a Phase II clinical trial evaluating the antitumor activity of intravenous PXD101, a small molecule histone deacetylase (HDAC) inhibitor, for the treatment of ovarian cancer. This trial is being sponsored by the National Cancer Institute (NCI) under a Clinical Trials Agreement with CuraGen for PXD101.
The Phase II trial is an open-label study being led by Dr. Amit Oza at Princess Margaret Hospital in Toronto, Canada. Patients with either advanced platinum resistant ovarian tumors or micropapillary/borderline low malignant potential (LMP) ovarian carcinoma may be enrolled for treatment with PXD101. Patients may have received no more than three prior lines of therapy. Upon enrollment, patients will receive intravenous PXD101 daily for five days in three week cycles until disease progression. The primary endpoint for the study is the determination of objective disease response, as evaluated by the RECIST criteria. Secondary endpoints include evaluation of safety and tolerability of PXD101, stable disease rates, duration of response, progression-free survival, as well as median and overall survival. Up to 62 patients at sites across Canada and the United States will be enrolled into the study.
“Hypoacetylation appears to play an important role in silencing the expression of genes, including tumor supressors that regulate cell survival, proliferation, and differentiation,” commented Dr. Oza. “The ability to reactivate tumor suppressor gene(s), together with the new published preclinical data, provides an excellent rationale to evaluate the role of the histone deacetylase inhibitor, PXD101 in treating two different populations of patients with ovarian cancer, those with advanced refractory tumors and those patients with micropapillary and borderline, or low malignant potential, tumors.”
“This NCI-sponsored trial evaluating PXD101 monotherapy complements our ongoing Phase Ib/II clinical trial, which is studying intravenous PXD101 in combination with paclitaxel and carboplatin for the treatment of advanced ovarian cancer. Both of these trials will generate data that will allow us to better understand the role of PXD101 in the treatment of this disease, and provide results to enable a decision regarding registrational development for ovarian cancer,” stated Dr. Timothy Shannon, Executive Vice President of Research and Development and Chief Medical Officer at CuraGen Corporation.
Correlative pharmacodynamic studies will also be conducted to evaluate the potential inhibition of HDACs in ovarian tumor cells from patients enrolled in this trial. Evaluation of the genes regulating proliferation and apoptosis (programmed cell death), as well as acetylation of histone and non-histone proteins, will be performed.
In an article published in the August 2006 issue of Molecular Cancer Therapeutics, CuraGen and TopoTarget scientists also reported new preclinical data for PXD101 that is relevant to ovarian cancer. Data in the study demonstrates that PXD101 has growth-inhibitory activity as mono- or combo therapy on multidrug resistant ovarian cancer lines, as well as on primary clinical cancer specimens grown in culture. Furthermore, PXD101 was found to have anti-tumor activity in animal models of ovarian cancer.
About Ovarian Cancer
Ovarian cancer causes a significant burden of disease accounting for 5% of all cancer deaths and is the fifth leading cause of death in women in Canada, the U.S., and Europe. Despite the efficacy of the combination of platinum/paclitaxel chemotherapy in advanced ovarian carcinoma, more than 75% of patients with stage III/IV disease ultimately relapse and die from their disease. Recurrent ovarian carcinoma is incurable and is treated with platinum-based therapy when the treatment free interval following initial therapy is longer than 6 months. Patients who have resistant ovarian cancer, whose disease does not respond to first line carboplatin and paclitaxel have a dire prognosis and the likelihood of response to further chemotherapy is very low (approximately 10%). There is therefore a need to develop new agents for the treatment of patients with this malignancy.
About PXD101
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, 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.
PXD101 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. In August 2004, CuraGen signed a Clinical Trials Agreement with the NCI under which the NCI is sponsoring 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 preclinical and nonclinical 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 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
This press release contains forward-looking statements that are subject to certain risks and uncertainties. These forward-looking statements include statements regarding future expectations, beliefs, intentions, goals, strategies, plans or prospects regarding the future, including statements about the expected benefits of PXD101, and our ability to generate data that will allow us to better understand the role of PXD101 in the treatment of ovarian cancer. 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.
CRGN-P Contact: Glenn Schulman, Pharm.D. Assistant Director of Investor Relations gschulman@curagen.com (888) 436-6642
CuraGen Corporation
CONTACT: Glenn Schulman, Pharm.D., Assistant Director of InvestorRelations of CuraGen Corporation, 888-436-6642, gschulman@curagen.com
