EntreMed, Inc, of Rockville, Maryland, announced at the Inflammation and Immune Diseases Drug Discovery and Development Summit held this month in New Brunswick, New Jersey, that daily oral administration (100 mg/kg) of its lead compound, 2-methoxyestradiol (2ME2) in rheumatoid arthritis (RA) resulted in a dose-dependent decrease in inflammation and tissue destruction in accepted preclinical animal models of RA. These findings further support the potential for 2ME2 as a disease-modifying antirheumatic drug (DMARD).

Disease progression was blocked by treatment with 2ME2 based on quantitative histological analyses of tissue from a collagen-induced arthritis model. Two parameters for assessing inflammatory responses—infiltration of leukocytes and pannus severity—showed a clear dose-dependent improvement with 2ME2 treatment. Cartilage lesion and bone resorption severity scores, two parameters that assess the extent of tissue destruction, also displayed a dose-dependent decline following treatment with 2ME2. Additional preclinical data were presented that demonstrated that the severity of arthritis development could be further attenuated by 2ME2 in combination with methotrexate.

The anti-arthritic activities of 2ME2 in preclinical models of RA were apparent in both preventive and treatment studies. When 2ME2 was administered in the preventive setting,
the onset of arthritis was delayed significantly. When 2ME2 was administered in the disease treatment setting, there was marked inhibition of tissue and joint damage. The beneficial effects of 2ME2 in these models were dose-dependent and nonimmunosuppressive.

Recently issued US Patent No. 7,012,070, titled "Estrogenic Compounds as Anti-Mitotic Agents," contains claims granted by the US Patent Office covering 2ME2 for the treatment of multiple indications, including inflammatory disorders such as RA. The patent claims cover methods of treating a broad range of disease indications with 2ME2 independent of mechanism. The patent is owned by Children's Hospital Boston and is licensed exclusively to EntreMed worldwide.

— A. Techman