BRANFORD, Conn., Nov. 10 /PRNewswire-FirstCall/ -- CuraGen Corporation and TopoTarget A/S (Copenhagen Stock Exchange: TOPO) today announced updated results from a Phase Ib trial of PXD101, a small molecule histone deacetylase (HDAC) inhibitor, in combination with carboplatin and paclitaxel in patients with advanced solid tumors, along with three additional posters on PXD101, were presented at the 18th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, being held November 7th to 10th in Prague, Czech Republic.
Updated results were presented in a poster entitled, “A Phase I Safety, Pharmacokinetic and Pharmacodynamic Study of Intravenously Administered PXD101 Plus carboplatin or paclitaxel or Both in Patients with Advanced Solid Tumors,” by Dr. Ulrik Lassen, Coordinating Investigator, Department of Oncology at the Finsen Center, Rigshospitalet, in Denmark. The data demonstrated that intravenous PXD101 was well tolerated when administered in combination with standard doses of carboplatin and paclitaxel, with no dose limiting toxicities (DLT) encountered and no Grade 4 adverse events noted. To date, 23 patients have been enrolled in the trial. Of these patients, evidence of clinical activity was noted in 2 patients (9%) achieving a partial response (one patient each with pancreatic and rectal cancer) and 10 patients (43%) achieving stable disease (SD) lasting from 2 to greater than 13 cycles. One ovarian cancer patient with SD also achieved a 73% reduction in CA-125 levels.
“In this trial, we found the combination of PXD101, paclitaxel, and carboplatin to be well tolerated and are very encouraged by the objective tumor responses noted in patients with advanced cancers,” commented Dr. Lassen. “During the Phase II portion of the study, we will continue to look for activity of the PXD101/carboplatin/paclitaxel combination in advanced ovarian cancer patients.”
The clinical trial was a Phase Ib open label, dose escalation study in patients with advanced solid tumors for which there is no standard therapy. The primary objective was to determine the maximum tolerated dose (MTD) and the dose limiting toxicities (DLT) of intravenous PXD101, in doses up to 1000 mg/m2/d, administered in combination with standard doses of carboplatin (AUC of 5) and paclitaxel (175 mg/m2). Following completion of the Phase Ib portion of the study, the trial has now advanced into Phase II. Fifteen patients will be enrolled to further evaluate the safety and activity of PXD101 combined with carboplatin and paclitaxel in patients with advanced ovarian cancer. Results from the Phase II trial are anticipated in mid-2007.
CuraGen and TopoTarget also announced that additional clinical and preclinical results with PXD101 were presented during poster sessions at the EORTC-AACR-NCI Symposium on Molecular Targets and Cancer Therapeutics including:
* “A Phase Ib safety and pharmacodynamic study of PXD101 alone and in combination with 5-fluorouracil in patients with advanced solid tumors.” PXD101 in combination with 5-FU was generally well-tolerated at doses of 1000 mg/m2/d PXD101 in combination with 250 mg/m2/d 5-FU. No dose-limiting toxicities or drug-related grade 3 or 4 adverse events have been observed. The most common adverse events included fatigue, nausea and vomiting, dysgeusia, dehydration and anorexia. The dose escalation portion of this trial is ongoing. Following completion of the dose escalation portion of the trial, an expansion of the study at the MTD in colorectal patients is planned with results anticipated by mid-2007; * “Biochemical characterization of PXD101, a small molecule HDAC inhibitor, and a library of additional compounds on recombinant class I and II HDAC isoforms.” The results in this poster presentation demonstrate that PXD101 potently inhibits eight recombinant, purified HDAC isoforms (four Class I and four Class II) with EC50s ranging from 30 to 216 nanomolar, thus establishing PXD101 as a pan inhibitor of histone deacetylases; and * “Activity of the histone deacetylase (HDAC) inhibitor PXD101 in preclinical prostate cancer studies.” The results in this poster presentation show that PXD101 inhibits the growth of prostate cancer cell lines in vitro at sub-micromolar IC50 concentrations. In addition, PXD101 demonstrated potent anti-tumor and anti-metastatic activity in an orthotopic PC-3 xenograft animal model.
Reprints of the poster presentations, as well as information about ongoing clinical trials with PXD101 are available on CuraGen’s website, http://www.curagen.com, or by emailing info@curagen.com.
About Ovarian Cancer
According to the American Cancer Society (ACS), ovarian cancer is the fourth leading cause of cancer death in women. It is estimated that, in 2006, more than 22,000 new cases of ovarian cancer will be diagnosed in the United States. Furthermore, nearly 70% of these women will be diagnosed with advanced, metastatic disease. Despite advances in therapeutic options, the mortality rate for ovarian cancer has not improved significantly over the past 50 years, with more than 16,000 women expected to die from ovarian cancer this year.
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 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 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 ability to obtain results from PXD101 clinical trials in 2007. 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, MPH Assistant Director of Investor Relations gschulman@curagen.com (888) 436-6642
CuraGen Corporation
CONTACT: Glenn Schulman, PharmD, MPH, Assistant Director of InvestorRelations at CuraGen Corporation, 888-436-6642, gschulman@curagen.com
