CuraGen Corporation
(Nasdaq: CRGN) and TopoTarget A/S announced today updated Phase II MM
results on PXD101, a small molecule histone deacetylase (HDAC) inhibitor,
were presented at the American Society of Hematology (ASH) Annual Meeting
in Orlando, Florida, December 10 to 13, 2006. Preliminary results on 21
evaluable patients with advanced MM demonstrated that PXD101 was
well-tolerated following intravenous administration, with patients
achieving clinical benefit from PXD101 in combination with dexamethasone.
The Phase II clinical trial results were presented in a poster
entitled, "A Phase II Study of PXD101 in Advanced Multiple Myeloma." The
Phase II clinical trial was an open label, multi-center study evaluating
the safety and activity 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 intravenous PXD101 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 enrolled had previously received a median of 6 prior
lines of therapy (range 2 - 10). Results indicate that 6 patients achieved
stable disease (SD) for at least 2 cycles on PXD101 monotherapy, 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
patients treated with this combination, an objective response rate of 50%
was achieved including 2 partial responses and 2 minimal responses. Four
additional patients achieved SD (range 2 - 15 cycles). PXD101, both alone
and in combination with dexamethasone, was generally well-tolerated.
"We found the level of clinical activity obtained with this HDAC
inhibitor, as well as the tolerability of PXD101 alone and in combination
with dexamethasone, promising and believe it is very supportive of further
evaluation of PXD101 in combination with other treatments to explore the
potential benefits for patients with advanced multiple myeloma," commented
Daniel Sullivan, M.D., Clinical Investigator for PXD101, Professor in the
Departments of Oncology, Medicine, and Biochemistry and Molecular Biology,
and Program Leader of Experimental Therapeutics, at the H. Lee Moffitt
Cancer Center & Research Institute in Tampa, Florida.
Presentations on preclinical results with PXD101 were also made at the
ASH Annual Meeting including an oral presentation and a second poster
presentation, both demonstrating increased activity of PXD101 against
multiple myeloma in vivo and in vitro when combined with Velcade(R)
(bortezomib) for Injection.
An oral presentation entitled, "Combination of the Proteasome Inhibitor
PS341 (Bortezomib) and a Histone Deacetylase Inhibitor PXD101 Results in
Stronger Inhibition of Multiple Myeloma and Osteoclastogenesis," was made
by Rentian Feng, Ph.D., Research Associate at the University of Pittsburgh
in the Division of Hematology and Oncology, during the Multiple Myeloma:
Bone Biology Session chaired by Suzanne Lentzch, M.D., Ph.D. Preclinical
results evaluating bortezomib in combination with PXD101 demonstrated that
the drug combination resulted in stronger inhibition of MM cell
proliferation and osteoclast formation than either drug used alone.
Osteoclasts play an important role in the disease as they cause painful
bone lesions in patients with MM.
A preclinical poster presentation 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," was also made by James Berenson, M.D., Medical & Scientific
Directors at the Institute for Myeloma & Bone Cancer Research. The data
showed that when mice bearing bortezomib-resistant human tumors were
treated with the combination of PXD101 and bortezomib, greater inhibition
of both tumor growth and circulating human IgG levels were observed than
when either drug was used alone. These results suggest that treatment with
PXD101 in combination with bortezomib may be an effective therapy for
bortezomib-resistant multiple myeloma.
"We are very pleased with the clinical and preclinical data on PXD101
presented this year at ASH," stated Timothy M. Shannon, M.D., Executive
Vice President of Research and Development and Chief Medical Officer at
CuraGen. "These results highlight the potential use of PXD101 in
combination with other therapies for the treatment multiple myeloma. These
data, along with the results being generated in the other 14 clinical
trials currently underway, will enable us to identify the most promising
indications for PXD101 during 2007 and initiate registrational studies
during 2008."
Reprints of the poster presentation, as well as information about
ongoing clinical trials are available on CuraGen's website,
curagen.
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 preclinical and
nonclinical studies on PXD101 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
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 plans to further
characterize the safety and activity of PXD101 in combination with other
treatments for MM. 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.
CuraGen Corporation
curagen