BRANFORD, Conn., Dec. 12 /PRNewswire-FirstCall/ -- CuraGen Corporation and TopoTarget A/S announced today updated Phase II MM results on PXD101, a small molecule histone deacetylase (HDAC) inhibitor, were presented at the American Society of Hematology (ASH) Annual Meeting in Orlando, Florida, December 10 to 13, 2006. Preliminary results on 21 evaluable patients with advanced MM demonstrated that PXD101 was well-tolerated following intravenous administration, with patients achieving clinical benefit from PXD101 in combination with dexamethasone.
The Phase II clinical trial results were presented in a poster entitled, "A Phase II Study of PXD101 in Advanced Multiple Myeloma." The Phase II clinical trial was an open label, multi-center study evaluating the safety and activity of intravenous PXD101 administered as a single-agent, and in combination with dexamethasone, on patients with advanced MM who had previously failed at least two treatment regimens. Patients were treated with at least two cycles of intravenous PXD101 and assessed for response. A total of 25 patients were enrolled in the study, of which 21 were eligible to be evaluated for single agent clinical activity. Patients enrolled had previously received a median of 6 prior lines of therapy (range 2 - 10). Results indicate that 6 patients achieved stable disease (SD) for at least 2 cycles on PXD101 monotherapy, with no objective responses observed.
Patients who progressed following treatment with PXD101 monotherapy were eligible to receive PXD101 in combination with dexamethasone. Of the 8 patients treated with this combination, an objective response rate of 50% was achieved including 2 partial responses and 2 minimal responses. Four additional patients achieved SD (range 2 - 15 cycles). PXD101, both alone and in combination with dexamethasone, was generally well-tolerated.
"We found the level of clinical activity obtained with this HDAC inhibitor, as well as the tolerability of PXD101 alone and in combination with dexamethasone, promising and believe it is very supportive of further evaluation of PXD101 in combination with other treatments to explore the potential benefits for patients with advanced multiple myeloma," commented Daniel Sullivan, M.D., Clinical Investigator for PXD101, Professor in the Departments of Oncology, Medicine, and Biochemistry and Molecular Biology, and Program Leader of Experimental Therapeutics, at the H. Lee Moffitt Cancer Center & Research Institute in Tampa, Florida.
Presentations on preclinical results with PXD101 were also made at the ASH Annual Meeting including an oral presentation and a second poster presentation, both demonstrating increased activity of PXD101 against multiple myeloma in vivo and in vitro when combined with Velcade(R) (bortezomib) for Injection.
An oral presentation entitled, "Combination of the Proteasome Inhibitor PS341 (Bortezomib) and a Histone Deacetylase Inhibitor PXD101 Results in Stronger Inhibition of Multiple Myeloma and Osteoclastogenesis," was made by Rentian Feng, Ph.D., Research Associate at the University of Pittsburgh in the Division of Hematology and Oncology, during the Multiple Myeloma: Bone Biology Session chaired by Suzanne Lentzch, M.D., Ph.D. Preclinical results evaluating bortezomib in combination with PXD101 demonstrated that the drug combination resulted in stronger inhibition of MM cell proliferation and osteoclast formation than either drug used alone. Osteoclasts play an important role in the disease as they cause painful bone lesions in patients with MM.
A preclinical poster presentation entitled, "Effects of a Novel Histone Deacetylase Inhibitor, PXD101, When Used as Monotherapy or in Combination with Bortezomib on Tumor Growth in a Mouse Model of Human Multiple Myeloma," was also made by James Berenson, M.D., Medical & Scientific Directors at the Institute for Myeloma & Bone Cancer Research. The data showed that when mice bearing bortezomib-resistant human tumors were treated with the combination of PXD101 and bortezomib, greater inhibition of both tumor growth and circulating human IgG levels were observed than when either drug was used alone. These results suggest that treatment with PXD101 in combination with bortezomib may be an effective therapy for bortezomib-resistant multiple myeloma.
"We are very pleased with the clinical and preclinical data on PXD101 presented this year at ASH," stated Timothy M. Shannon, M.D., Executive Vice President of Research and Development and Chief Medical Officer at CuraGen. "These results highlight the potential use of PXD101 in combination with other therapies for the treatment multiple myeloma. These data, along with the results being generated in the other 14 clinical trials currently underway, will enable us to identify the most promising indications for PXD101 during 2007 and initiate registrational studies during 2008."
Reprints of the poster presentation, as well as information about ongoing clinical trials are available on CuraGen's website, http://www.curagen.com, or by emailing info@curagen.com.
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-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 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. An oral formulation of PXD101 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 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 is headquartered in Branford, Connecticut. For additional information please visit http://www.curagen.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 plans to further characterize the safety and activity of PXD101 in combination with other treatments for MM. 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 Contacts: CuraGen Corporation Glenn Schulman, PharmD gschulman@curagen.com (888) 436-6642
CuraGen CorporationCONTACT: Glenn Schulman, PharmD, of CuraGen Corporation, +1-888-436- 6642,gschulman@curagen.com
