"The emerging clinical results from our PXD101 clinical development program are very encouraging. We believe these results, along with data being generated by the NCI-sponsored trials, will enable us to define the most efficient path toward registration," commented Dr. Timothy Shannon, Executive Vice President of R&D and Chief Medical Officer. "The level of activity noted with PXD101, in combination with commonly used chemotherapy agents for patients with advanced cancers, highlights the competitiveness of our HDAC development program. We look forward to presenting clinical data in a peer-reviewed fashion at medical conferences later this year and throughout 2007. Based on these and additional data from the PXD101 development program, we expect to make decisions in 2007 regarding which indications will be advanced into registrational development during 2008."
Phase Ib/II trial of PXD101 in combination with paclitaxel/carboplatin for advanced solid tumors
The Phase Ib portion of this trial aimed to establish the maximum tolerated dose (MTD) of intravenous PXD101 in combination with carboplatin and paclitaxel with advanced solid tumors for which there is no standard therapy. CuraGen and TopoTarget announced today that the Phase Ib dose escalation portion of this trial has been completed. A total of 23 patients were treated with preliminary results indicating that PXD101 was well tolerated when combined with standard full doses of paclitaxel and carboplatin, widely used treatments for a variety of cancers. Clinical activity was noted including 2 partial objective responses in patients with advanced, refractory cancer (confirmed response in a patient with pancreatic cancer and an ongoing confirmation in a patient with metastatic rectal cancer), and 3 patients achieving stable disease (SD) lasting greater than 10 cycles of treatment (one patient each with advanced Ewing's sarcoma, malignant melanoma and bladder cancer). Further results from the Phase Ib trial will be presented in November at the 18th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Prague, Czech Republic. This study has now advanced into the Phase II portion and will enroll 15 patients 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.
Phase II trial of PXD101 monotherapy and in combination with dexamethasone for advanced multiple myeloma (MM)
The Phase II clinical trial was an open label, multi-center study evaluating the safety and efficacy 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 PXD101 monotherapy 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 had previously received an average of greater than 5 prior lines of therapy before enrollment into the study. Preliminary results indicate that 9 patients (43%) receiving PXD101 monotherapy achieved SD, 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 evaluable patients treated with this combination an objective response rate of 38% was achieved including 1 partial response and 2 minimal responses. The other 5 patients achieved SD, with two of these patients continuing to receive PXD101 and dexamethasone. PXD101, both alone and in combination with dexamethasone, was well-tolerated. Single agent activity did not meet the criteria necessary for expansion of enrollment into this trial. Currently enrolled patients will continue to receive PXD101 in combination with dexamethasone. Updated results from this trial will be presented in December at the 2006 American Society of Hematology Annual Meeting.
CuraGen and TopoTarget will await preliminary results from an ongoing program evaluating PXD101 in combination with Velcade(R) (bortezomib) for Injection, as well as data being generated from other ongoing trials with PXD101, before initiating additional investments in MM.
Phase Ib/II trial of PXD101 in combination with 5-fluorouracil (5-FU) for advanced solid tumors
The Phase Ib portion of this trial aims to establish the MTD of intravenous PXD101 in combination with 5-FU, on patients with advanced solid tumors for which there is no standard therapy. Based on initial results, 5-FU 250mg/m2/day was well tolerated with 1000 mg/m2/d PXD101, and additional cohorts have been added to the trial to evaluate higher doses of 5-FU in combination with PXD101. To date, a total of 17 patients have been enrolled in the study, with enrollment complete in four out of five cohorts. Preliminary results from the Phase Ib dose-escalation portion of the study will be presented in November at the 18th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Prague, Czech Republic. The trial is expected to advance into Phase II during the first quarter 2007. Approximately 20 patients with advanced colorectal cancer will be enrolled to further evaluate the safety and activity of the regimen, with results anticipated in mid-2007.
CuraGen and TopoTarget Sponsored Clinical Trials with PXD101 In addition to the above mentioned trials, CuraGen and TopoTarget are conducting three additional clinical trials with PXD101.
* A Phase II clinical trial evaluating intravenous PXD101 for the treatment of T-cell non-Hodgkin's lymphomas (NHL) including cutaneous T-cell lymphoma (CTCL), as well as peripheral and other T-cell NHL. Results from this trial are expected by the end of 2007; * A Phase Ib clinical trial evaluating intravenous PXD101 in combination with Velcade(R) for Injection for the treatment of advanced MM. Results from this study are anticipated by mid-2007; and * A Phase I clinical trial evaluating the safety and tolerability of oral PXD101 for the treatment of advanced solid tumors. Results from this trial are anticipated by the end of 2007. NCI-sponsored Clinical trials with PXD101
A total of seven clinical trials have been initiated by the National Cancer Institute (NCI) under a Clinical Trials Agreement signed with CuraGen. These trials include:
* A Phase II clinical trial evaluating PXD101 for the treatment of Acute Myelogenous Leukemia (AML); * A Phase II clinical trial evaluating PXD101 for the treatment of B-cell lymphomas; * A Phase II clinical trial evaluating PXD101 for the treatment of mesothelioma; * A Phase I/II clinical trial evaluating PXD101 for the treatment of inoperable hepatocellular cancer; * A Phase I clinical trial evaluating PXD101 in combination with cis-retinoic acid for the treatment of patients with advanced solid tumors; * A Phase I clinical trial evaluating in combination with Velcade(R) (bortezomib) for Injection for the treatment of advanced malignancies, including solid tumors and lymphomas; and * A Phase I clinical trial evaluating PXD101 in combination with azacitidine for the treatment of advanced hematologic malignancies. Conference Call Details and Dial-in Information
Date: Thursday, October 26, 2006 Time: 11:00 a.m. ET Dial-in: 877-272-5391 (domestic) 706-758-4315 (international) Passcode: 8562032
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.
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 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.
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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, our ability to obtain results from PXD101 clinical trials in 2007 and our ability to advance one or more products into registational development by 2008. 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.
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