CuraGen Corporation
(Nasdaq: CRGN) and TopoTarget A/S (Copenhagen Stock Exchange: TOPO)
announced today the initiation of patient dosing in a Phase II open-label,
multi-center clinical trial evaluating the efficacy and safety of
intravenous belinostat (PXD101), a small molecule histone deacetylase
(HDAC) inhibitor, in combination with Velcade(R) (bortezomib) for
Injection, in multiple myeloma patients refractory to or who have rapidly
relapsed from at least one previous bortezomib-containing regimen.
Based on preliminary safety results from ongoing Phase Ib trials
evaluating belinostat in combination with bortezomib, CuraGen and
TopoTarget have initiated this Phase II trial in multiple myeloma patients.
The Phase II clinical trial is being led by James Berenson, M.D., Principal
Investigator, Medical & Scientific Director at the Institute for Myeloma &
Bone Cancer Research, and will be conducted at multiple sites across the
U.S. Up to 35 patients are planned for study enrollment with preliminary
results anticipated by the end of 2007.
"Based on our preclinical studies that showed markedly increased anti-
myeloma effects when belinostat was combined with bortezomib to treat a
bortezomib-resistant myeloma in immunodeficient mice, we look forward to
enrolling bortezomib-resistant multiple myeloma patients into this Phase II
trial and determining whether the combination can provide clinical benefit
to multiple myeloma patients that have failed, or who have relapsed on
bortezomib therapy," commented Dr. Berenson.
"Emerging safety results from CuraGen and NCI clinical trials that are
evaluating belinostat and bortezomib have shown the combination to be
generally well-tolerated. Therefore, we have initiated this Phase II study
to allow relapsed and/or refractory multiple myeloma patients the ability
to receive treatment with belinostat and bortezomib, and anticipate
reporting preliminary results from the study by the end of the year,"
commented Frank Armstrong, M.D., President and Chief Executive Officer of
CuraGen. "As data continues to be generated from our Phase II trials in
ovarian cancer, colorectal cancer, and T-cell lymphomas, we look forward to
presenting preliminary results during mid-2007, and remain on track to
initiate a Phase III program during 2008 and advance belinostat towards
registration."
In vitro studies published in the literature have shown that HDAC
inhibitors and bortezomib, when combined, act synergistically through
independent mechanisms leading to enhanced killing of cancer cells. During
the 2006 ASH Annual Meeting, preclinical results evaluating belinostat in
combination with bortezomib were presented in a poster 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." The data suggest that when mice bearing
bortezomib-resistant human tumors were treated with the combination of
belinostat and bortezomib, greater inhibition of both tumor growth and
circulating human IgG levels were observed than when either drug was used
alone, and the mice tolerated the combination well without obvious adverse
effects. These results suggest that treatment with belinostat in
combination with bortezomib may be an effective therapy for
bortezomib-resistant multiple myeloma.
As this Phase II study of belinostat and bortezomib begins, CuraGen
will close enrollment in their ongoing Phase Ib study of this combination
in multiple myeloma. The NCI-sponsored trial evaluating this combination on
patients with advanced solid tumors remains open for enrollment.
About Multiple Myeloma
Multiple myeloma (MM) is a progressive cancer arising from a particular
type of blood cell, called plasma cells. It is the second most prevalent
blood cancer in the U.S. with nearly 50,000 individuals suffering from MM,
and more than 15,000 new cases expected to be diagnosed this year. MM is
characterized by excessive numbers of abnormal plasma cells in the bone
marrow and the overproduction of abnormal immunoglobulins. As a result of
MM, patients may develop bone lesions, anemia, elevated blood calcium
levels, kidney damage, and a decreased ability to fight off infections.
Despite the availability of treatments for MM, there is currently no cure
for this disease.
About Belinostat
Belinostat 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 belinostat 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 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.
About CuraGen
CuraGen Corporation (Nasdaq: CRGN) 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 curagen.
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 topotarget.
Safe Harbor
Statements in this press release regarding management's future
expectations, beliefs, intentions, goals, strategies, plans or prospects,
including statements relating to the expected benefits of belinostat in
combination with Velcade(R) (bortezomib) for Injection, and the potential
results of the clinical trials with belinostat designed to evaluate such
benefits, 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 September 30, 2006,
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.
CuraGen Corporation
curagen