Replies to post #2764 on Entremed (ENMD)

[reason4]

Press Release Source: EntreMed, Inc.

New Patents Strengthen EntreMed Position in Cancer and Inflammation
Wednesday August 17, 8:30 am ET
Two Patents Cover Broad Uses of 2ME2 as Anti-Angiogenic Drugs

ROCKVILLE, Md., Aug. 17 /PRNewswire-FirstCall/ -- EntreMed, Inc. (Nasdaq: ENMD - News), a clinical-stage pharmaceutical company developing therapeutics for the treatment of cancer and inflammation, today announced the issuance of two U.S. patents covering its lead clinical-stage compound, 2- methoxyestradiol (2ME2) and multiple derivatives of 2ME2. 2ME2 (Panzem® Capsules and Panzem® NCD) is currently in clinical trials for cancer, as well as in preclinical development for inflammatory disorders.
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(Logo: http://www.newscom.com/cgi-bin/prnh/20010620/ENMDLOGO )

The patents grant EntreMed intellectual property protection for 2ME2 and derivatives of 2ME2 in oncology and a broad range of non-oncology indications, including inflammatory disorders, immune disorders, cardiovascular disorders, and rheumatoid arthritis.

2ME2 is a novel anticancer agent, which is part of a next generation of antimitotic cancer drugs that bind to tubulin and work through multiple cellular pathways. 2ME2 can attack tumors on multiple fronts -- directly by disrupting microtubules, an intracellular matrix necessary for the rapid division of cancer cells (mitosis), by inducing programmed cell death (apoptosis), and by blocking blood vessels that feed tumors (angiogenesis inhibition).

James S. Burns, EntreMed President & CEO, commented, "EntreMed is focused on the development of a new generation of small molecule drugs for the treatment of cancer and inflammatory disorders by attacking disease cells directly and the blood vessels that nourish them. These patents strengthen our position in next generation tubulin and angiogenesis inhibitors for the treatment of cancer and expand the range of indications for our lead anti- angiogenic agents."

Mr. Burns further commented, "We have increasing evidence that 2ME2 has both antitumor and antiinflammatory properties. Recent preclinical studies have demonstrated the potential for 2ME2 as a disease modifying anti-rheumatic drug (DMARD) candidate. As a result, we have the potential to expand the clinical indications for 2ME2 into both oncology (Panzem® NCD) and rheumatoid arthritis. These patents cover both indications and a broad range of other 2ME2 anti-angiogenic indications. Our goal is to continue strengthening EntreMed's intellectual property for its key product candidates, and to acquire additional technology and products that reinforce our focus on multi-mechanism drugs."

U.S. Patent No. 6,930,128 entitled "Estrogenic Compounds as Anti-Mitotic Agents," claims the use of 2-methoxyestradiol and derivatives of 2- methoxyestradiol for treatment of a wide variety of diseases that are angiogenesis mediated in a dosage sufficient to inhibit cell division and discloses novel compounds derived from 2-methoxyestradiol that inhibit microtubule formation, tubulin polymerization, and/or tubulin depolymerization.

Patent 6,930,128 further claims the use of 2-methoxyestradiol and derivatives of 2-methoxyestradiol for treating diseases or conditions selected from solid tumors, tumor metastasis, benign tumors, hemangiomas, atherosclerosis, abnormal wound healing, inflammatory disorders, immune disorders, rheumatoid arthritis, ocular neovascularization, macular degeneration and gynecological disorders with compounds having certain structural modifications of 2-methoxyestradiol.

U.S. Patent No. 6,908,910 entitled "Estrogenic Compounds as Anti-Mitotic Agents," which issued in June 2005, represents a further enhancement of patent claims to the use of 2-methoxyestradiol for treatment of a wide variety of ophthalmic diseases that are angiogenesis mediated. The patent claims methods for treating diseases or conditions with compounds having certain structural modifications of 2-methoxyestradiol. Both patents are owned by Children's Hospital Boston and licensed exclusively to EntreMed.

About EntreMed

EntreMed, Inc. (Nasdaq: ENMD - News) is a clinical-stage pharmaceutical company developing therapeutic candidates primarily for the treatment of cancer and inflammation. Panzem® (2-methoxyestradiol or 2ME2), the Company's lead drug candidate, is currently in clinical trials for cancer, as well as in preclinical development for non-oncology indications. EntreMed's goal is to develop and commercialize new compounds based on the Company's expertise in angiogenesis, cell cycle regulation and inflammation -- processes vital to the treatment of cancer and other diseases, such as rheumatoid arthritis. Additional information about EntreMed is available on the Company's website at http://www.entremed.com and in various filings with the Securities and Exchange Commission.

[C_Peptide]

2ME2 conjugation

Conjugation is the modification of a molecule by enzymatic attachment to some particular molecular entity. There is a family of enzymes called glucuronidases which tag molecules that fit a certain profile with a glucuronide group. This group is then recognized by the kidney as being something to eliminate into the urine. It is part of how toxins and hormones which have done their job are eliminated from the body.

You can think of 2ME2 molecules as attendees at a dance performance, and glucuronidase enzymes as the doormen at the auditorium entrance who hand out programs, which represent glucuronide. The auditorium is the bloodstream, the doormen are the intestinal lining, and the lobby is the gut. For everyone to get a program, they have to make sure they don't pass from the lobby to the auditorium faster than the doormen can hand out programs. Panzem NCD's quick dissolution is like a rush of attendees who don't all get programs. Smaller particles can potentially dissolve and diffuse faster than the gut lining can attach glucuronide to the 2ME2.

Here is where the analogy breaks down, because at intermission, when the blood passes through the kidneys, the ushers drag everyone holding a program through the lighted emergency exits at either side of the stage and kick them to the street. Only those who didn't get programs get to stay for the second half. That is why the NCD formula gets to see more of the show.

As for what the 2ME2 and 2ME1 abbreviations mean, they describe modifications of estradiol (E2) to 2-methoxyestradiol (2ME2) and 2-methoxyestrone (2ME1). The 2 at the end of 2ME2 stands for "-diol", meaning two hydroxyl (or alcohol) groups, one at the "2 position" that has been subsequently O-methylated (the 2ME part), and one at the "17-beta position". When 2ME2 is oxidized to 2ME1 by 17-beta hydroxysteroid dehydrogenase, the hydroxyl group (-O-H) becomes a ketone group (=O), and the 1 signifies that the molecule is now a derivative of estrone (E1) with only 1 hydroxyl group. These are just abbreviated organic chemistry naming conventions. You can think of 17-beta HSD enzymes at the "ketone cops" of estrogen metabolism, running around trying to keep estrogen from being too, ...well, ... estrogenic.

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C-Peptide