BRANFORD, Conn., Nov. 18 /PRNewswire-FirstCall/ -- CuraGen Corporation and TopoTarget A/S (Copenhagen Stock Exchange: TOPO) today announced updated interim Phase I data on PXD101, a small molecule histone deacetylase (HDAC) inhibitor being developed for the treatment of solid and hematologic tumors, were presented yesterday at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, November 14th to 18th, 2005 in Philadelphia, PA.
In a poster entitled, "A Phase 1 Pharmacokinetic (PK) and Pharmacodynamic (PD) study of the Histone Deacetylase (HDAC) Inhibitor PXD101 in Patients with Advanced Solid Tumors," interim data on 42 patients receiving PXD101 as a single-agent treatment for advanced solid tumors were reported and suggest PXD101 is well-tolerated following intravenous administration and may have potential anti-tumor activity. Pharmacokinetic data from the initial assessment of orally administered PXD101 were also presented.
The ongoing Phase I open-label study was designed to determine the safety, maximum-tolerated dose (MTD), pharmacokinetics, and pharmacodynamics of intravenously administered PXD101. PXD101 was administered as a single-agent to patients with advanced solid tumors whose disease was refractory to standard therapy or for whom no standard therapy existed.
The most common adverse events were fatigue, nausea, vomiting and phlebitis. No significant hematological toxicities were noted. Clinical investigators described toxicities as mild with no grade 4 toxicity observed. Based on the dose-escalation safety data, the dose for Phase II monotherapy efficacy studies was determined to be 1000 mg/m2. Pharmacokinetic analysis of PXD101 demonstrates dose-proportional plasma levels and an elimination half- life of approximately one hour. Histone hyperacteylation, a biomarker of the activity of PXD101 on its target, was noted to increase proportionally with dose escalation, and lasted from 6 to 24 hours after administration. Initial pharmacokinetic assessment of orally administered PXD101 showed that PXD101 had an oral bioavailability of approximately 33% with PXD101 plasma concentrations exceeding levels required for in vitro activity.
As of November 1, 2005, potential anti-tumor activity has been observed in two patients receiving PXD101 for more than one year. Following single-agent treatment with PXD101, an epithelial T-cell thymoma patient exhibited 70% reduction of mediastinal disease and a patient with metastatic alveolar sarcoma has had stable disease for 13 months. Two additional patients, with a diagnosis of metastatic fibrosarcoma and breast cancer, have had stable disease for six months and four months, respectively.
"We are very pleased with the updated Phase I results reported with PXD101 as a single-agent treatment on cancer patients with advanced solid tumors. This data indicates that both intravenous and oral dosing are potential routes of administration for PXD101, and that we may be seeing possible anti-tumor activity," stated Timothy M. Shannon, M.D., Executive Vice President Research and Development and Chief Medical Officer at CuraGen. "We look forward to also reporting updated results on our ongoing Phase I study of patients with advanced hematologic cancers at the 2005 American Society of Hematology (ASH) Annual Meeting in December. In addition to these two ongoing Phase I studies, the development program for PXD101 also includes three proof-of-concept trials evaluating this HDAC inhibitor as a potential treatment for multiple myeloma, colorectal, and ovarian cancers. We anticipate reporting preliminary Phase II results for our multiple myeloma trial by mid-2006, and Phase Ib colorectal and ovarian cancer results by the end of 2006."
The Companies also reported that additional preclinical data on PXD101 were presented in two separate poster sessions at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics.
"Activity of the histone deacetylase (HDAC) inhibitor PXD101 in preclinical ovarian cancer studies." Data generated by researchers at CuraGen and TopoTarget suggest that PXD101 has anti-cancer activity in vitro and in vivo against ovarian cancer cell lines as a single-agent. Furthermore, PXD101 exhibited additive to synergistic activity when combined with other chemotherapeutic agents, including carboplatin and paclitaxel. This poster was presented on Wednesday, November 16, 2005. PXD101 is currently being evaluated in a Phase Ib clinical trial in combination with carboplatin and/or paclitaxel for the treatment of advanced solid tumors, including ovarian cancer. Preliminary results from this study are expected to be available in the fourth quarter of 2006.
"Gene profiling of PXD101, a novel hydroxamate type inhibitor of histone deacetylase, leads to identification of Aurora kinase inhibition." Researchers at the National Cancer Institute (NCI) reported data on PXD101 and one of its potential mechanisms of action. PXD101's ability to inhibit histone deacetylase results in inhibition of aurora kinase, a pathway believed to be involved in tumorigenesis. This poster was presented on Thursday, November 17, 2005.
Reprints of the poster presentation and published abstracts, 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 HDAC inhibitors
A growing body of research highlights the role of histone deacetylases (HDAC) in regulating gene expression, particularly the expression of cancer- related genes. 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 phenotype when used in combination with other anti-cancer agents. HDAC inhibitors are believed to play a role in a wide range of solid malignancies such as breast, colon, lung and ovarian cancers, and hematological malignancies, such as lymphomas, leukemias and myeloma.
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 the Company's pipeline of products for unmet medical needs. The Company is headquartered in Branford, CT. For additional information please visit http://www.curagen.com.
About TopoTarget
TopoTarget (CSE: TOPO) is a publicly listed biopharmaceutical company based in Denmark, UK and Germany, dedicated to finding answers to cancer and developing improved therapies with a strong focus on cancer patient needs. The company both develops novel pharmaceutical compounds and identifies new indications for existing drugs, combining its broad and in-depth understanding of the molecular mechanisms of cancer with a wide experience in clinical oncology practice. Having grown both organically and through acquisitions/in- licensing, TopoTarget has built substantial platforms in HDAC and topoisomerase II inhibitors as well as a clinical pipeline comprising eight programmes with the most advanced drug candidate in regulatory review. TopoTarget is also establishing its own specialist sales force in Europe. For more information, please refer to http://www.topotarget.com.
Safe Harbor
This press release contains forward-looking statements including statements about the potential anti-tumor activity of PXD101, the ability of PXD101 to be administered by IV and orally, the availability of updated results of CuraGen's ongoing Phase I study of patients with advanced hematologic cancers in December, CuraGen's anticipation that it will report preliminary Phase II multiple myeloma results by mid-2006 and Phase Ib colorectal and ovarian cancer results by the end of 2006, and CuraGen's expectation that preliminary results of its Phase Ib study of PXD101 in combination with carboplatin and/or paclitaxel will be available in the fourth quarter of 2006. 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 genomics-based pharmaceutical 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 Quarterly Report on Form 10-Q for the period ended September 30, 2005 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.
Contacts: CuraGen Corporation Glenn Schulman, PharmD, MPH gschulman@curagen.com (888) 436-6642
CuraGen CorporationCONTACT: Glenn Schulman, PharmD, MPH of CuraGen Corporation,+1-888-436-6642, gschulman@curagen.com
