EntreMed Presents MKC-1 and ENMD-1198 Preclinical Data at AACR Annual Meeting
Compounds Demonstrate Potent Antitumor Activity in a Variety of Tumor Types
ROCKVILLE, MD, April 16, 2008 â€“ EntreMed, Inc. (Nasdaq: ENMD), a clinical-stage pharmaceutical company developing therapeutics for the treatment of cancer and inflammatory diseases, today announced the presentation of preclinical results for two of its clinical stage compounds, MKC-1 and ENMD-1198. Presentations were given by EntreMed scientists during two poster sessions at the American Association for Cancer Research (AACR) Annual Meeting being held this week in San Diego, California.
MKC-1 administered in combination with paclitaxel in a preclinical, orthotopic breast tumor model demonstrated synergistic tumor inhibition. The combination of MKC-1 and paclitaxel, but neither agent alone, demonstrated tumor regression of the bulky breast cell line tumors grown in this model. In addition, the combination decreased angiogenesis and proliferation, and increased apoptosis as early as 4 days post treatment. Treatment with the combination also decreased the oncogenic proteins HIF-1Î±, pAKT, and pS6 ribosomal proteins.
In a second presentation, treatment of the 1A9 human ovarian carcinoma cell line with ENMD-1198 induced cell cycle arrest and decreased levels of the oncogenic transcription factor proteins HIF-1Î±, pSTAT3, and pNFÎºB. Treatment with ENMD-1198 also downregulates expression of several tubulin isotypes in 1A9 cells, but not in ENMD-1198-resistant (1A9-1198R) cells. This, combined with the relative lack of inhibition of oncogenic proteins observed in 1A9-1198R cells, suggests interaction with tubulin may be important for the modulation of oncogenic proteins by ENMD-1198. In summary, data demonstrate that ENMD-1198 resistant 1A9 cells may provide a useful tool for evaluating a pharmacogenomic profile that can be correlated with clinical benefit.
Dr. Bray commented on the presentations, â€œWe continue to see encouraging potent preclinical antitumor activity with MKC-1 and ENMD-1198. Although both compounds are currently in multiple clinical trials in oncology, these robust preclinical data further support and strengthen our knowledge of their mechanisms of action. Development of MKC-1 and ENMD-1198 is in line with the Companyâ€™s focus on orally available, small molecule drugs for the treatment of cancer and inflammatory diseases. MKC-1 is currently in multiple Phase 1 and 2 clinical trials and ENMD-1198 is in a Phase 1 study in advanced cancers. Additional clinical studies are planned for both compounds in 2008.â€
To view a copy of the poster presentations, visit Scientific Presentations under the Therapeutic Pathways section of the Companyâ€™s web site at www.entremed.com.
EntreMed, Inc. is a clinical-stage pharmaceutical company developing therapeutic candidates primarily for the treatment of cancer and inflammation. MKC-1 is currently in multiple Phase 2 clinical trials for cancer. MKC-1 is an oral cell-cycle regulator with activity against the mTOR pathway. ENMD-1198, a novel antimitotic agent, and ENMD-2076, a selective kinase inhibitor, are in Phase 1 studies in advanced cancers. The Company also has an approved IND application for PanzemÂ® in rheumatoid arthritis. EntreMed’s goal is to develop and commercialize new compounds based on the Company’s expertise in angiogenesis, cell-cycle regulation and inflammation â€“ processes vital to the treatment of cancer and other diseases, such as rheumatoid arthritis. Additional information about EntreMed is available on the Companyâ€™s web site at www.entremed.com and in various filings with the Securities and Exchange Commission.
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