Pancreatica News Abstracts Archive - Millennium Researchers Announce Preclinical Findings of its Proteasome Inhibitor MLN341 Against Several Solid Tumor Types

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Millennium Researchers Announce Preclinical Findings of its Proteasome Inhibitor MLN341 Against Several Solid Tumor Types
--Investigational compound's unique mechanism of action may also help overcome resistance to chemotherapy--

CAMBRIDGE, Massachuetts, April 8, 2002

Millennium Pharmaceuticals, Inc. today announced findings of a preclinical trial of its investigational drug, MLN341 (formerly known as LDP- 341 and PS-341), studying its effects with different chemotherapies against a variety of solid tumors in mice. The results, announced at the annual meeting of the American Association for Cancer Research (AACR) in San Francisco, CA, demonstrated that MLN341, when combined with chemotherapy, consistently caused greater decreases in tumor size than either treatment given alone.

MLN341 is designed to specifically block proteasomes, which are enzymes in the cell responsible for breaking down a variety of proteins, including many that regulate cell division. Laboratory studies suggest that by inhibiting the proteasome, MLN341 in cancer cells disrupts the regulating proteins and ultimately encourages apoptosis (programmed cell death).

"MLN341 may be a promising therapy for a variety of cancers because its unique mechanism of action, inhibition of the proteasome, affects multiple molecular pathways important to the survival of many different tumor types,'' said Julian Adams, Ph.D., Millennium's senior vice president, drug discovery. "Essentially, inhibiting the proteasome in cancer cells halts cell division, eventually resulting in cancer cell death. However, unlike traditional chemotherapy, which harms cancer cells and healthy cells alike, healthy cells appear to be able to recover from the effects of proteasome inhibition, while cancer cells seem to be irreversibly committed to programmed cell death.''

In preliminary data from a phase II clinical trial of MLN341 used as a single agent in patients with relapsed and refractory multiple myeloma, a cancer of the blood, the progression of the disease was halted in 85% of study participants. Those receiving the new therapy experienced manageable side effects, including fatigue, diarrhea, decreased platelets and peripheral neuropathy.

Study findings

In preclinical studies, MLN341 was tested in combination with a variety of common chemotherapies -- irinotecan (Camptosar®), fluorouracil (5FU), docetaxel (Taxotere®), cisplatin (Platinol®), and paclitaxel (Taxol®) -- against various human solid tumors that had been grown as xenografts in mice. These xenografts included colon, pancreatic, ovarian and prostate cancer. The effectiveness of each MLN341/chemotherapy combination was compared with MLN341 alone and each respective chemotherapeutic agent alone. In every case, the MLN341/chemotherapy combination reduced tumor size by a significantly greater amount than either agent alone. For example:

MLN341 with Camptosar® reduced colon tumors in mice by 65 percent relative to either agent alone;
MLN341 and Platinol® reduced ovarian tumors in mice by 60 percent relative to either agent alone;
MLN341 and Taxol® reduced prostate tumors in mice by 50 percent to 60 percent relative to either agent used alone.
In addition to the reduction in tumor size, mice generally appeared to tolerate the combination therapies as well as single agent treatments.

Other preliminary data presented at the AACR meeting showed the potential for MLN341 to reduce the growth of several experimental pancreatic tumor models which respond poorly to standard chemotherapy.

-- In a preclinical study of mice injected with bladder cancer cells that
were resistant to the chemotherapy drug gemcitabine (Gemzar(R)),
researchers tested the effectiveness of MLN341 in combination with
Gemzar(R) versus either agent alone. The MLN341/ Gemzar(R) combination
significantly reduced the growth of bladder tumors compared with either
of the drugs alone (p<0.05). Combination therapy reduced the
production of certain substances expressed by the bladder tumors that
promote cancerous spread (metastasis) and help nourish the tumors, such
as vascular endothelial cell growth factor (VEGF), interleukin-8 (IL-
8), and matrix metalloproteinase type 9 (MMP-9).

Millennium's Oncology Franchise

Millennium has committed to pursing oncology as a core franchise area, dedicating significant resources and capabilities in the areas of technology, scientific expertise and strategic business development. To this end, Millennium has already produced a deep oncology pipeline that ranges from multiple novel targets to commercialized therapeutic and diagnostic products. Among the most advanced clinical compounds in addition to MLN341 are MLN591, an anti-PSMA antibody currently in phase I clinical trials for advanced prostate cancer and MLN576, a small molecule with DNA-binding activity in phase I trials for solid and hematologic tumors. MLN518, a first-in-class RTK inhibitor, is expected to enter phase I trials for acute myeloid leukemia later this year. The CAMPATH® (alemtuzumab) monoclonal antibody, a therapeutic developed from a former joint venture of Millennium, is commercially available in both the United States and a number of European countries. A Millennium alliance partner and licensee is in the process of developing and commercializing Melastatin(TM), a melastatin detection product for melanoma developed through our predictive medicine efforts.

About Millennium

Millennium Pharmaceuticals, Inc., a leading biopharmaceutical company, applies its comprehensive and integrated science and technology platform for the discovery and development of breakthrough therapeutic and predictive medicine products with a goal of delivering personalized medicine. Millennium is primarily focusing its research, development and commercialization activities in four key areas: cardiovascular, oncology, inflammation and metabolic diseases. Through the industrialization of its gene-to-patient platform, Millennium is striving to accelerate the process of drug discovery and development. Headquartered in Cambridge, Mass., Millennium currently employs more than 2,000 people.

Camptosar® is a trademark of Pharmacia Corporation. Platinol®and Taxol® are trademarks of Bristol-Myers Squibb. Gemzar® is a trademark of Eli Lilly and Company.

This press release contains "forward-looking statements,'' including statements about our growth and future operating results, discovery and development of products, potential acquisitions, strategic alliances and intellectual property. Various risks may cause Millennium's actual results to differ materially, including: adverse results in our drug discovery and clinical development processes; failure to obtain patent protection for our discoveries; commercial limitations imposed by patents owned or controlled by third parties; our dependence upon strategic alliance partners to develop and commercialize products and services based on our work; difficulties or delays in obtaining regulatory approvals to market products and services resulting from our development efforts; and the requirement for substantial funding to conduct research and development and to expand commercialization activities. For a further list and description of the risks and uncertainties we face, see the reports we have filed with the Securities and Exchange Commission. We disclaim any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.

Press Release
SOURCE: Millennium Pharmaceuticals, Inc.

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	Pancreas Cancer News and Archives
		For educational purposes only; not to be relied upon. Please read Pancreatica Disclaimer
	Millennium Researchers Announce Preclinical Findings of its Proteasome Inhibitor MLN341 Against Several Solid Tumor Types --Investigational compound's unique mechanism of action may also help overcome resistance to chemotherapy-- CAMBRIDGE, Massachuetts, April 8, 2002 Millennium Pharmaceuticals, Inc. today announced findings of a preclinical trial of its investigational drug, MLN341 (formerly known as LDP- 341 and PS-341), studying its effects with different chemotherapies against a variety of solid tumors in mice. The results, announced at the annual meeting of the American Association for Cancer Research (AACR) in San Francisco, CA, demonstrated that MLN341, when combined with chemotherapy, consistently caused greater decreases in tumor size than either treatment given alone. MLN341 is designed to specifically block proteasomes, which are enzymes in the cell responsible for breaking down a variety of proteins, including many that regulate cell division. Laboratory studies suggest that by inhibiting the proteasome, MLN341 in cancer cells disrupts the regulating proteins and ultimately encourages apoptosis (programmed cell death). "MLN341 may be a promising therapy for a variety of cancers because its unique mechanism of action, inhibition of the proteasome, affects multiple molecular pathways important to the survival of many different tumor types,'' said Julian Adams, Ph.D., Millennium's senior vice president, drug discovery. "Essentially, inhibiting the proteasome in cancer cells halts cell division, eventually resulting in cancer cell death. However, unlike traditional chemotherapy, which harms cancer cells and healthy cells alike, healthy cells appear to be able to recover from the effects of proteasome inhibition, while cancer cells seem to be irreversibly committed to programmed cell death.'' In preliminary data from a phase II clinical trial of MLN341 used as a single agent in patients with relapsed and refractory multiple myeloma, a cancer of the blood, the progression of the disease was halted in 85% of study participants. Those receiving the new therapy experienced manageable side effects, including fatigue, diarrhea, decreased platelets and peripheral neuropathy. Study findings In preclinical studies, MLN341 was tested in combination with a variety of common chemotherapies -- irinotecan (Camptosar®), fluorouracil (5FU), docetaxel (Taxotere®), cisplatin (Platinol®), and paclitaxel (Taxol®) -- against various human solid tumors that had been grown as xenografts in mice. These xenografts included colon, pancreatic, ovarian and prostate cancer. The effectiveness of each MLN341/chemotherapy combination was compared with MLN341 alone and each respective chemotherapeutic agent alone. In every case, the MLN341/chemotherapy combination reduced tumor size by a significantly greater amount than either agent alone. For example: MLN341 with Camptosar® reduced colon tumors in mice by 65 percent relative to either agent alone; MLN341 and Platinol® reduced ovarian tumors in mice by 60 percent relative to either agent alone; MLN341 and Taxol® reduced prostate tumors in mice by 50 percent to 60 percent relative to either agent used alone. In addition to the reduction in tumor size, mice generally appeared to tolerate the combination therapies as well as single agent treatments. Other preliminary data presented at the AACR meeting showed the potential for MLN341 to reduce the growth of several experimental pancreatic tumor models which respond poorly to standard chemotherapy. -- In a preclinical study of mice injected with bladder cancer cells that were resistant to the chemotherapy drug gemcitabine (Gemzar(R)), researchers tested the effectiveness of MLN341 in combination with Gemzar(R) versus either agent alone. The MLN341/ Gemzar(R) combination significantly reduced the growth of bladder tumors compared with either of the drugs alone (p<0.05). Combination therapy reduced the production of certain substances expressed by the bladder tumors that promote cancerous spread (metastasis) and help nourish the tumors, such as vascular endothelial cell growth factor (VEGF), interleukin-8 (IL- 8), and matrix metalloproteinase type 9 (MMP-9). Millennium's Oncology Franchise Millennium has committed to pursing oncology as a core franchise area, dedicating significant resources and capabilities in the areas of technology, scientific expertise and strategic business development. To this end, Millennium has already produced a deep oncology pipeline that ranges from multiple novel targets to commercialized therapeutic and diagnostic products. Among the most advanced clinical compounds in addition to MLN341 are MLN591, an anti-PSMA antibody currently in phase I clinical trials for advanced prostate cancer and MLN576, a small molecule with DNA-binding activity in phase I trials for solid and hematologic tumors. MLN518, a first-in-class RTK inhibitor, is expected to enter phase I trials for acute myeloid leukemia later this year. The CAMPATH® (alemtuzumab) monoclonal antibody, a therapeutic developed from a former joint venture of Millennium, is commercially available in both the United States and a number of European countries. A Millennium alliance partner and licensee is in the process of developing and commercializing Melastatin(TM), a melastatin detection product for melanoma developed through our predictive medicine efforts. About Millennium Millennium Pharmaceuticals, Inc., a leading biopharmaceutical company, applies its comprehensive and integrated science and technology platform for the discovery and development of breakthrough therapeutic and predictive medicine products with a goal of delivering personalized medicine. Millennium is primarily focusing its research, development and commercialization activities in four key areas: cardiovascular, oncology, inflammation and metabolic diseases. Through the industrialization of its gene-to-patient platform, Millennium is striving to accelerate the process of drug discovery and development. Headquartered in Cambridge, Mass., Millennium currently employs more than 2,000 people. Camptosar® is a trademark of Pharmacia Corporation. Platinol®and Taxol® are trademarks of Bristol-Myers Squibb. Gemzar® is a trademark of Eli Lilly and Company. This press release contains "forward-looking statements,'' including statements about our growth and future operating results, discovery and development of products, potential acquisitions, strategic alliances and intellectual property. Various risks may cause Millennium's actual results to differ materially, including: adverse results in our drug discovery and clinical development processes; failure to obtain patent protection for our discoveries; commercial limitations imposed by patents owned or controlled by third parties; our dependence upon strategic alliance partners to develop and commercialize products and services based on our work; difficulties or delays in obtaining regulatory approvals to market products and services resulting from our development efforts; and the requirement for substantial funding to conduct research and development and to expand commercialization activities. For a further list and description of the risks and uncertainties we face, see the reports we have filed with the Securities and Exchange Commission. We disclaim any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise. Press Release SOURCE: Millennium Pharmaceuticals, Inc.

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