BRANFORD, Conn., March 22 /PRNewswire-FirstCall/ -- CuraGen Corporation and TopoTarget A/S (Copenhagen Stock Exchange: TOPO) announced today the initiation of patient dosing in a Phase Ib/II proof-of-concept trial to evaluate PXD101, a small molecule histone deacetylase (HDAC) inhibitor, in combination with Velcade(R) (bortezomib) for the treatment of relapsed, refractory multiple myeloma, a deadly form of blood cancer. Preliminary results from this open-label, multi-center study are expected by mid-2007.
The goal of the Phase Ib portion of this trial is to establish the maximum tolerated dose (MTD) of PXD101 in combination with Velcade(R) in up to 30 patients who have failed at least two prior lines of therapy for multiple myeloma. Following determination of the MTD, the study will enter Phase II and enroll up to 15 additional patients with relapsed, refractory multiple myeloma who have failed at least one prior therapy. The Phase II portion of the study will further evaluate the safety, pharmacokinetics, pharmacodynamics, and anti-tumor activity of PXD101 in combination with Velcade(R). Patients will be enrolled at multiple sites in the United States.
“In laboratory studies, PXD101 has shown synergistic activity against multiple myeloma cells in vitro when combined with Velcade(R). In addition, Phase I results suggest that PXD101 is well tolerated and the safety profile does not appear to have any significant overlapping toxicities with Velcade(R),” stated Seema Singhal, M.D., Professor of Medicine at the Feinberg School of Medicine at Northwestern University in Chicago, and Principal Investigator. “Based upon these results, we are very interested in evaluating the safety and activity of this intriguing combination for patients with multiple myeloma.”
In vitro studies published in the literature have shown that HDAC inhibitors and Velcade(R) act through independent mechanisms that lead to enhanced killing of multiple myeloma cells when combined. In preclinical studies, PXD101 demonstrated growth-inhibitory activity against a variety of multiple myeloma cell lines at nanomolar concentrations. PXD101 also showed synergistic activity when combined with Velcade(R) against multiple myeloma during in vitro studies. These data support the evaluation of PXD101 in combination with Velcade(R) for the treatment of multiple myeloma.
“Preclinical studies suggest that HDAC inhibition plays a complementary role with Velcade(R), and our internal research demonstrates that PXD101 has a synergistic effect with Velcade(R) against multiple myeloma. This Phase Ib/II trial will evaluate the safety and potential activity of the combined regimen and we anticipate that preliminary results will be available by mid-2007,” stated Timothy M. Shannon, M.D., Executive Vice President of Research and Development, and Chief Medical Officer at CuraGen.
About Multiple Myeloma
Multiple myeloma (MM) is a progressive cancer arising from a particular type of blood cell, called plasma cells. It is the second most prevalent blood cancer in the U.S. with nearly 50,000 individuals suffering from MM, and more than 15,000 new cases expected to be diagnosed this year. MM is characterized by excessive numbers of abnormal plasma cells in the bone marrow and the overproduction of abnormal immunoglobulins. As a result of MM, patients may develop bone lesions, anemia, elevated blood calcium levels, kidney damage, and a decreased ability to fight off infections. Despite the availability of treatments for MM, there is currently no cure for this disease.
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. 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-cell lymphoma, 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 National Cancer Institute (NCI) under which the NCI will sponsor several additional 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 signed 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 of the therapy.
About CuraGen
CuraGen Corporation is a biopharmaceutical company dedicated to improving the lives of patients by developing a pipeline of novel protein, antibody, and small molecule therapeutics in the areas of oncology, inflammatory diseases, and diabetes. CuraGen has established broad development alliances with Abgenix, TopoTarget, and Bayer, and its experienced preclinical and clinical teams are advancing its pipeline of products for unmet medical needs. CuraGen is headquartered in Branford, Connecticut. For additional information please visit http://www.curagen.com.
About TopoTarget
TopoTarget (CSE: TOPO) is a fully integrated biopharmaceutical company, headquartered in Denmark and with subsidiaries in the UK and Germany, and dedicated to finding “Answers for Cancer” and developing improved cancer therapies. The company 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 is on key cancer enzyme regulators (mainly HDAC and topoisomerase II inhibitors) and a strong development foundation of proprietary, highly predictive cancer models has been built. TopoTarget has a broad portfolio of small molecule preclinical drug candidates and eight drugs are in clinical development, consisting of both novel anti- cancer therapeutics and the development of new cancer indications for existing drugs. The most advanced drug candidate, Savene(TM) for extravasations is expected to be launched end 2006. In addition to organic growth, TopoTarget consistently looks for opportunities to strengthen and expand its activities through acquisitions and in-licensing. In selected markets, an own specialist oncology sales force is being established. For more information, please refer to http://www.topotarget.com.
Safe Harbor
This press release contains forward-looking statements including statements about CuraGen’s expectation that preliminary results from the Phase Ib/II clinical trial will be available in mid-2007; CuraGen’s anticipation of a successful completion of the Phase Ib portion of the trial; enrollment in the Phase Ib and Phase II portions of the trial; and NCI’s sponsorship of clinical trials for 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 drug development programs of CuraGen and/or TopoTarget 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 Report on Form 10-K for the year ended December 31, 2006 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) is a registered trademark of Millennium Pharmaceuticals, Inc. 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, +1-888-436-6642, gschulman@curagen.com
Web site: http://www.curagen.com//
