>>BOSTON & SAN DIEGO--(BUSINESS WIRE)--Dec. 7, 2004-- GlycoGenesys, Inc., (Nasdaq: GLGS - News), a biotechnology company focused on carbohydrate-based drug development, announced today that an in vitro study showed for the first time that its lead drug candidate, GCS-100LE, triggered cell death in both B-cell malignant cell lines and primary cancer cells taken from patients with chronic lymphocytic leukemia (CLL). GCS-100LE, currently in a Phase I dose escalation trial for solid tumors, is a novel carbohydrate-based compound being developed for the treatment of solid tumors and multiple myeloma. Data from the new study was presented last evening by world-renowned cancer researcher and GlycoGenesys collaborator, Dr. Finbarr E. Cotter of Barts School of Medicine, London, at the American Society of Hematology (ASH) 46th Annual Meeting and Exposition in a poster session on Lymphoma Therapy - New Biologic Agents. The poster was titled "GCS-100, a Galectin 3 Antagonist, Is a Novel Caspase-9 Apoptosis Activating Agent for the Treatment of Indolent B-Cell Malignancies."
Dr. Cotter's Poster Presentation Highlights
GCS-100LE was found to:
Induce significant apoptosis (cell death) in both malignant B-cell lines and in primary patient chronic lymphocytic leukemia cells in vitro with minimal effect against normal B-cells and stem cell cultures.
Greatly enhance the apoptotic effect of chemotherapy at low doses, even in the presence of high levels of anti-apoptotic proteins such as Bcl-2.
Induce cell death in B-cell malignancies including chronic lymphocytic leukemia via caspase-9, a known apoptotic pathway utilized by approved chemotherapy agents. Activation of caspase-9 has been shown to predict a good anti-cancer response in B-cell malignancies.
These findings lay the framework for clinical evaluation of GCS-100LE in B-cell malignancies, especially for potential treatment of chronic lymphocytic leukemia.
The Study
The study investigated the mechanism by which GCS-100LE induces apoptosis (programmed cell death) in indolent B-cell lymphomas. It found that GCS-100LE induced apoptosis in malignant cell lines as well as in primary cells from patients with chronic lymphocytic leukemia with minimal effect on normal B cells. Notably, low doses of GCS-100LE significantly enhanced the effect of chemotherapy in these cancer cells. GCS-100LE was found to induce a specific apoptotic pathway, the mitochondrial caspase-9 pathway. The apoptotic effect of GCS-100LE occurred even in the presence of the protein Bcl-2, a natural inhibitor of cell death, which confers resistance to widely used chemotherapy drugs in several cancers. GCS-100LE has been previously shown to bind to Galectin-3, a protein that generally has a higher expression in B-cell cancers. This may be the cause of GCS-100LE's targeting of malignant B-cells.
Dr. Finbarr Cotter, GlycoGenesys' collaborator and primary author of the study abstract said, "Our recent study shows for the first time that GCS-100LE has strong activity against primary cancer cells taken from patients with chronic lymphocytic leukemia. In these primary cells and in other B-cell cancer cell lines, GCS-100LE works through a specific caspase-dependent apoptotic pathway. Moreover, other studies have shown that GCS-100LE can activate additional beneficial anti-cancer mechanisms. These attributes of GCS-100LE suggest its application in several different types of cancer and its combination with chemotherapeutic agents that work through complementary pathways for a potential synergistic or additive therapeutic effect. I am keen to commence clinical studies based on this preclinical work."
Bradley J Carver, President and CEO of GlycoGenesys, a secondary author of the study abstract, further commented, "Our poster presentations at this year's annual meeting of the American Society of Hematology underscore the clinical rationale and versatility of GCS-100LE to be developed for potential treatment of several bloodborne cancers. We are encouraged by Dr. Cotter's recent findings. They provide solid scientific rationale for expanding the clinical development of GCS-100LE beyond our current programs in solid tumor and multiple myeloma.
About Indolent B-cell Malignancies
In the U.S., over 320,000 people are estimated to have some form of B-cell malignancy and each year approximately 55,000 new cases and 20,000 deaths occur from these cancers. Between 80% and 85% of non-Hodgkin's lymphomas are of B-cell origin. Indolent B-cell malignancies include chronic lymphocytic leukemia, follicular lymphoma and B-cell non-Hodgkin's lymphoma as well as other lymphomas. They are low-grade or slow-growing lymphomas that permit long survival periods but are continuously recurring and virtually incurable in advanced stages. Current treatment options are characterized by low-cure rates due to the slow-growing nature of these lymphomas. Patients without symptoms are monitored closely for development of symptoms including tumor masses and major organ involvement. At such times, treatment is started.
About GCS-100LE
GCS-100LE is a novel carbohydrate compound with potential application in solid tumors and bloodborne cancers. Independent research has shown that Galectin-3, a key target of GCS-100LE is implicated in several cellular activities. GCS-100LE has at least three mechanisms of action: it may induce apoptosis, or programmed cell death; appears to interfere with angiogenesis, the process by which cancer cells recruit a blood supply from the body in order to proliferate; and appears to interfere with a process called cellular adhesion, which plays a key role in metastasis, or the spread of cancer beyond the primary tumor. Galectin-3 has high expression in many cancers, but not in normal cells, conferring broad potential applications for GCS-100LE in solid and bloodborne cancers. GCS-100 has been evaluated at low dose levels in previous clinical trials for patients with colorectal, pancreatic and other types of solid tumors. GCS-100LE, a low ethanol formulation, is currently in a dose escalation Phase I trial for solid tumors with Phase I and II clinical trials for multiple myeloma planned in 2005. <<
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Cheers, Tuck |
