CuraGen and TopoTarget Announce Presentation of Belinostat Clinical Trial Results at AACR-NCI-EORTC International Conference- Significant anti-tumor activity of combination IV belinostat in ovarian cancer reported -
BRANFORD, Conn., Oct. 25 /PRNewswire-FirstCall/ -- CuraGen Corporation , a clinical-stage biopharmaceutical company focused on oncology, and TopoTarget A/S (Copenhagen Stock Exchange: TOPO) announced today that four posters discussing clinical trial results with belinostat were presented at the 2007 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, San Francisco, CA. Data reported included Phase II clinical trial results on intravenous belinostat in combination with carboplatin and paclitaxel for relapsed ovarian cancer, Phase I safety and dose-escalation results for oral belinostat, and data from two NCI-sponsored clinical trials including Phase II results evaluating intravenous belinostat monotherapy for the treatment of ovarian cancers and Phase I results of belinostat in combination with bortezomib for advanced tumors.
CLN-8: Phase II Multicenter Trial of Belinostat (PXD101) in Combination with Carboplatin and Paclitaxel (BelCaP) for Patients with Relapsed Ovarian Cancer
Phase II results for CLN-8 were presented by Neil J. Finkler, MD, FACOG, FACS, Investigator and Director of the Gynecologic Oncology Program at Florida Hospital Cancer Institute in Orlando. At the time of the poster presentation, data were available on 23 patients including efficacy data for 16 patients who had available pre- and post-baseline assessments of tumor. The dose regimen (referred to as BelCaP) of intravenous (IV) belinostat 1000 mg/m2/d in combination with carboplatin AUC = 5 and paclitaxel 175 mg/m2, was well- tolerated.
Reduction in tumor size was seen in 15 of 16 patients by radiologic assessment. To date, objective response has been observed in 8 patients, including 2 partial responses confirmed by RECIST and 6 additional responses that are pending radiologic confirmation. At the time of presentation, 13 additional patients have treatment ongoing with continued radiologic assessment of tumor to determine best response. Activity and responses have been observed in patients with platinum sensitive and platinum resistant disease. CuraGen also announced today that trial has reached the target enrollment.
"We are very encouraged by the level of activity we have seen with BelCaP for the treatment of relapsed ovarian cancer, including activity against platinum resistant tumors," commented Dr. Finkler. "We look forward to continuing to treat those patients currently on study and further defining the efficacy of BelCaP in the treatment of this disease."
"The activity of belinostat in preclinical ovarian studies, either alone or in combination with carboplatin and paclitaxel and in platinum sensitive and platinum resistant cell lines, represents some of the most compelling preclinical data we have developed with belinostat and we are pleased to see it translating into potential clinical benefit for patients with relapsed ovarian cancer," said Dr. Timothy Shannon, President and Chief Executive Officer of CuraGen. "We look forward to collecting the remaining data in this study and working with our advisors to determine a potential registrational path forward for IV belinostat in the treatment of ovarian cancer."
NCI-Sponsored Phase II trial Belinostat in Patients with Refractory or Relapsed Platinum Resistant Epithelial Ovarian Tumors (EOC) and Micropapillary/Borderline (LMP) Ovarian Tumors
Data was reported from a Phase II trial evaluating the activity of IV belinostat monotherapy in two ovarian cancer populations that had received up to three prior lines of chemotherapy: patients with Micropapillary/Borderline (LMP) ovarian tumors or patients with refractory or relapsed platinum resistant (progression within 6 months of last platinum treatment) Epithelial Ovarian Tumors (EOC). Primary endpoints of the study were objective response. Secondary endpoints included stable disease rate, survival, tolerability and assessment of molecular changes with therapy. Tumor response was assessed by RECIST and CA-125 criteria every two cycles. This Phase II trial is an open- label study being led by Dr. Amit Oza at Princess Margaret Hospital in Toronto, Canada. The clinical trial is being sponsored by the NCI under a Clinical Trials Agreement with CuraGen for belinostat.
During the poster presentation it was reported that 12 patients with LMP tumors received a median of 4 treatment cycles (range 1 to 13). To date, one LMP patient achieved a partial response (PR), one patient had a CA125 response, nine had SD, and two were not evaluable. Six patients remain on study. Objective responses to belinostat monotherapy were not observed in a heavily pre-treated well-defined platinum-resistant population of patients with EOC. Belinostat was safe and generally well-tolerated in these two ovarian cancer populations.
Dr. Shannon further commented, "We are very encouraged by the level of activity reported with IV belinostat monotherapy against these types of ovarian cancer. We believe that these results support and complement the CuraGen BelCaP activity data in relapsed ovarian cancer."
CLN-9: A Phase I Study of Oral Belinostat (PXD101) in Patients with Advanced Solid Tumors
Initial clinical trial results from the ongoing Phase I study evaluating oral belinostat for the treatment of solid tumors were presented by Dr. Rhoda Molife and Dr. Jooern Ang, investigators at the Royal Marsden Hospital, Sutton, United Kingdom. The Phase I trial is being led by Dr. W. Kevin Kelly, Associate Professor of Medicine in the Section of Medical Oncology and head of The Prostate & Urologic Oncology Program at the Yale Cancer Center, New Haven, CT.
The Phase I study is an open-label, multi-center dose-escalation trial designed to establish the maximum tolerated dose (MTD) for oral belinostat administered once or twice daily in one of two regimens (either continuous daily dosing or dosing days one through 14 in a 21-day cycle). Primary objectives for the study include evaluation of the safety, tolerability and pharmacokinetics of oral belinostat. Secondary objectives include assessment of the pharmacokinetic profile of oral belinostat administered once or twice daily at various dose levels and evaluation of anti-tumor activity. Comprehensive serial ECGs to evaluate the effect of belinostat on QTc interval were also performed.
At the time of the poster presentation, data were available on 60 patients enrolled into the dose-escalation study with 46 patients on the continuous daily regimen and 14 patients dosed days one through 14 in a 21-day cycle. Patients received a median of two treatment cycles (range 1 - 11) with fifteen patients ongoing. The most frequent adverse events reported were fatigue, anorexia and nausea. More than 2400 ECGs were collected in this trial, with no grade 3 or 4 QTc changes noted.
During the study, 15 patients (25%) achieved SD for greater than or equal to 12 weeks, with no RECIST-defined objective responses currently reported. Dose-escalation performed with 250 mg capsules of oral belinostat resulted in a presumptive continuous dosing MTD of 250 mg twice daily. The MTD for dosing of oral belinostat on days one through 14 in a 21-day cycle has not yet been reached. The investigators concluded that oral belinostat has been safe and well-tolerated at doses that may provide flexibility to complement the intravenous formulation of belinostat which is currently in Phase II development.
NCI-sponsored Phase I trial of Belinostat in Combination with Bortezomib in Patients with Advanced Solid Tumors and Lymphoma
Data on 17 patients, of which 14 were evaluable, were reported from this ongoing dose-escalation trial. The primary objective of the trial was evaluation of the safety profile and determination of the MTD of belinostat in combination with bortezomib for patients with advanced solid tumors or lymphomas, which are refractory to standard therapies or for which no standard treatment exists. Secondary endpoints included pharmacokinetics (PK), biological markers and anti-tumor activity. This Phase I trial is an open- label, dose-escalation study being led by Dr. S. Gail Eckhardt, Director of the Developmental Therapeutics and GI Malignancies Programs and Professor of Medicine at the University of Colorado Health Sciences Center. This trial is being sponsored by the NCI under a CTA with CuraGen for belinostat, and under a Cooperative Research and Development Agreement (CRADA) with Millennium Pharmaceuticals Inc. for bortezomib.
The investigators concluded that intravenous belinostat and bortezomib were well tolerated in combination at doses up to 600 mg/m2 belinostat and 1.3 mg/m2 bortezomib, with ongoing enrollment of patients into this dosing cohort. Activity of the combination reported included one patient with Ewing's Sarcoma that has maintained SD for 4 cycles, and two patients, one with peritoneal and one with appendiceal carcinoma, that have maintained SD for 3 cycles. Adverse events were generally grades 1-2 and reversible. No grade 4 non-hematologic toxicities were reported.
Conference Call Details and Dial-in Information Date: Thursday, October 25, 2007, 2007 Time: 5:00 p.m. Eastern time Dial-in: 877-272-5391 (domestic) 706-758-4315 (international) Passcode: 21928842 Webcast: Access to the live webcast and presentation are available at http://www.curagen.com
A replay of the conference call will be available starting at 8:00 p.m. Eastern time on Thursday, October 25, 2007 through Sunday, November 25, 2007 by dialing 800-642-1687 (domestic) or 706-645-9291 (international). The passcode for the replay is 21928842. An archive of the webcast will also be accessible at http://www.curagen.com.
Belinostat is a small molecule HDAC inhibitor being investigated for its role in the treatment of a wide range of solid tumors and hematologic malignancies either as a single-agent, or in combination with other active anti-cancer agents, including 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 belinostat is currently being evaluated in multiple clinical trials as a potential treatment for cutaneous and peripheral T-cell lymphomas, B-cell lymphomas, AML, mesothelioma, soft tissue sarcoma, MDS, and liver, colorectal, and ovarian cancers, either alone or in combination with anti- cancer therapies. An oral formulation of belinostat 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 belinostat 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 belinostat in order to better understand its anti-tumor activity and to provide supporting information for clinical trials.
CuraGen Corporation is a dedicated clinical-stage biopharmaceutical company developing diverse approaches for the treatment of cancer including belinostat and CR011-vcMMAE. By leveraging drug development strengths cultivated over the years, CuraGen expects to make a difference by advancing its promising therapeutics to address the unmet medical needs of cancer patients. CuraGen Corporation is headquartered in Branford, Connecticut. For additional information please visit http://www.curagen.com.
TopoTarget (OMX - The Nordic Exchange: TOPO) is a biopharmaceutical company, headquartered in Denmark and with subsidiaries in the UK, Germany and the USA, 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.
Statements in this press release regarding management's future expectations, beliefs, intentions, goals, strategies, plans or prospects, including statements relating to CuraGen's belinostat programs, including the results of its Phase I and Phase II clinical trials, the quality of data from such trials, the clinical benefits to patients and the potential for future registration and commercialization may constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements can be identified by terminology such as "anticipate," "believe," "could," "could increase the likelihood," "estimate," "expect," "intend," "is planned," "may," "should," "will," "will enable," "would be expected," "look forward," "may provide," "would" or similar terms, variations of such terms or the negative of those terms. Such forward-looking statements involve known and unknown risks, uncertainties and other factors including the risk that any one or more of CuraGen's drug development programs 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, CuraGen's stage of development as a biopharmaceutical company, government regulation and healthcare reform, technological uncertainty and product development risks, product liability exposure, uncertainty of additional funding, CuraGen's history of incurring losses and the uncertainty of achieving profitability, reliance on research collaborations and strategic alliances, competition, patent infringement claims against CuraGen's products, processes and technologies, CuraGen's ability to protect its patents and proprietary rights and uncertainties relating to commercialization rights, as well as those risks, uncertainties and factors referred to in the Company's Quarterly Report on Form 10-Q for the quarter ended June 30, 2007, filed with the Securities and Exchange Commission under the section "Risk Factors," as well as other documents that may be filed by CuraGen from time to time with the Securities and Exchange Commission. As a result of such risks, uncertainties and factors, the Company's actual results may differ materially from any future results, performance or achievements discussed in or implied by the forward-looking statements contained herein. CuraGen is providing the information in this press release as of this date and assumes no obligations to update the information included in this press release or revise any forward-looking statements, whether as a result of new information, future events or otherwise.
Contacts: Glenn Schulman, PharmD Director of Investor Relations (888) 436-6642 CRGN-Pgschulman@curagen.com
CONTACT: Glenn Schulman, PharmD, Director of Investor Relations of CuraGenCorporation, +1-888-436-6642, email@example.com
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Posted: October 2007
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