CuraGen Corporation
(Nasdaq: CRGN) announced preliminary data from an ongoing Phase II
trial of CR011-vcMMAE, an antibody-drug conjugate that targets GPNMB, for
the treatment of patients with unresectable Stage III or Stage IV melanoma.
Dr. Patrick Hwu, Co-Principal Investigator, and Professor and Chairman of
the Department of Melanoma Medical Oncology, at The University of Texas M.
D. Anderson Cancer Center, presented the data during an oral session at the
2008 International Society for Biologic Therapy of Cancer (iSBTc) Annual
Meeting.
Thirty-six patients were enrolled into this Phase II open-label,
multi-center trial that is evaluating the efficacy and safety of
CR011-vcMMAE 1.88 mg/kg administered intravenously once every three weeks.
Eligible patients had progressive disease at trial entry and may have
received one prior cytotoxic regimen and any number of prior
immunotherapies. Of the patients enrolled, 94% had Stage IV disease of
which two-thirds were classified as M1c, the poorest risk group.
At the time of the data cutoff for this analysis (19 Sept 2008), 31
patients had at least one efficacy assessment available, and 18 patients
were continuing to receive ongoing treatment in the study. The median
overall progression-free survival (PFS) to date was approximately 4.5
months. RECIST-defined partial responses were reported in 3 patients, 2
ongoing, and an unconfirmed partial response in 1 patient. Nineteen
patients had stable disease, 14 ongoing, with tumor shrinkage observed in
12 of these patients.
"PFS is a clinically meaningful and important regulatory endpoint. The
apparent prolongation in PFS of 4.5 months, compared to a historical
expectation of 1.7 months, combined with clear objective responses and
tumor reduction in the majority of patients, suggests that CR011-vcMMAE has
the potential to become an important novel therapy in this patient
population," commented Dr. Timothy Shannon, President and Chief Executive
Officer of CuraGen.
As expected based upon the expression of GPNMB and as observed in Phase
I, dermatologic adverse events consisting of rash, alopecia, and pruritus
were the most common toxicities in this study. A preliminary exploratory
analysis assessing the relationship of rash and PFS was performed and
showed a trend toward longer PFS in patients that developed Grade 2 or
higher rash (n=13). Other adverse events included fatigue, diarrhea,
anorexia and nausea. Grade 3 or 4 neutropenia was observed in 7 patients
(22%).
"The target of CR011-vcMMAE, GPNMB, is a protein that is believed to be
over expressed in a variety of tumors and also present in some normal
tissue including the skin. The preliminary data which may suggest a
correlation between the development of rash and clinical efficacy is very
intriguing and we will continue to assess its potential role in helping to
identify those patients who may best respond to treatment with
CR011-vcMMAE," commented Dr. Ronit Simantov, Chief Medical Officer at
CuraGen. "We would like to thank our investigators for their enthusiasm,
which we believe is highlighted by their ability to fully enroll this Phase
II trial in just 6 months, and we look forward to reporting the final data
from this Phase II trial during the first half of 2009."
"Targeting GPNMB with this antibody-drug conjugate represents a
potentially novel way to treat this disease, and based on these preliminary
Phase II results, CR011-vcMMAE appears to be clinically active against
unresectable melanoma in some patients. We look forward to further
evaluating the correlation between rash and clinical activity, as well as
alternate dosing schedules of CR011-vcMMAE," commented Dr. Hwu.
CuraGen is currently enrolling patients into a Phase I portion of this
trial to evaluate more frequent dosing schedules of CR011-vcMMAE, including
a weekly and a two out of every three-week regimen, to explore if more
frequent administration can provide additional activity in patients with
metastatic melanoma. CR011-vcMMAE is also being studied in an ongoing Phase
II trial in patients with metastatic breast cancer who have received
previous chemotherapy. CuraGen anticipates providing updated data from the
ongoing melanoma and breast cancer studies in the first half of 2009.
"While we continue to finalize data from this study, develop data from
more frequent dosing in patients with metastatic melanoma and from the
Phase II study in patients with breast cancer, we will be engaging in
discussions with potential partners as we develop plans for the advanced
stages of development," added Dr. Shannon. "The goal of a partnership will
be to support the financial, development and commercial resources that will
be required in advanced development, improving the risk profile to CuraGen
shareholders while maintaining upside potential."
In addition to M. D. Anderson, other sites participating in the
melanoma trial include Yale Cancer Center, New Haven, CT; The Angeles
Clinic and Research Institute, Santa Monica, CA; and New York University
Medical Center, New York, NY.
About CR011-vcMMAE
CR011-vcMMAE is an antibody-drug conjugate (ADC) being developed by
CuraGen that consists of a fully-human monoclonal antibody, CR011, linked
to a potent cell-killing drug, monomethyl-auristatin E (MMAE). The ADC
technology, comprised of MMAE and a stable linker system for attaching it
to CR011, was licensed from Seattle Genetics, Inc. (Nasdaq: SGEN). The ADC
is designed to be stable in the bloodstream. Following intravenous
administration, CR011-vcMMAE targets and binds to GPNMB, a specific protein
that is predominantly expressed on the surface of cancer cells, including
melanoma, breast cancer and gliomas. Upon internalization into the targeted
cell, CR011-vcMMAE is designed to release MMAE from CR011 to produce a
cell-killing effect. CR011-vcMMAE is currently in two Phase II trials
assessing the safety and efficacy in the treatment of melanoma and for the
treatment of metastatic breast cancer, and in a Phase I trial to evaluate
the safety and activity of alternate dosing schedules.
About Melanoma
According to the American Cancer Society, it is expected that
approximately 60,000 new cases of melanoma will be diagnosed, including
nearly 11,000 patients diagnosed with Stage III or Stage IV disease, and an
estimated 8,000 people in the U.S. will die of the disease during 2008. The
prognosis for patients with advanced melanoma is poor, and studies have
shown that the median survival is less than nine months.
About CuraGenCuraGen Corporation (Nasdaq: CRGN) is a clinical-stage
biopharmaceutical company developing promising approaches for the treatment
of cancer. CuraGen Corporation is headquartered in Branford, Connecticut.
For additional information please visit curagen.
Forward Looking Statements
Statements in this press release regarding management's future
expectations, beliefs, intentions, goals, strategies, plans or prospects,
including statements relating to CuraGen's development program for
CR011-vcMMAE, including CuraGen's ability to advance CR011-vcMMAE through
Phase II clinical trials for melanoma and metastatic breast cancer, explore
additional doses and schedules of this antibody-drug conjugate, explore the
potential of CR011-vcMMAE in a patient population in need of new therapies,
and intention to engage in discussions with potential partners with respect
to CR011-vcMMAE 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 CuraGen's pursuit
of partnership opportunities will not proceed as planned or 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, as well as risk associated with 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 ability to comply
with Nasdaq listing requirements, 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 under the section "Risk Factors" in CuraGen's
Quarterly Report on Form 10-Q for the quarter ended June 30, 2008, filed
with the Securities and Exchange Commission 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, CuraGen'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
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