EntreMed, Inc, of Rockville, Maryland, announced the issuance of US Patent No. 6,995,278, covering compositions and methods for treating mammalian diseases characterized by undesirable angiogenesis, by administering derivatives of 2-methoxyestradiol (2ME2, or Panzem®). The patent grants EntreMed composition-of-matter intellectual property protection through 2020 for analogs of 2ME2 in inflammatory and immune disorders, oncology, and other diseases characterized by abnormal mitosis or abnormal angiogenesis.

2ME2 is an orally bioavailable compound in preclinical development for inflammatory disorders and is currently in clinical trials for cancer. 2ME2 has multiple mechanisms of action, including the inhibition of angiogenesis, microtubule formation, hypoxia inducible factor-1 alpha (HIF-1α, a protein required for cell survival under stress), and bone resorption. Apoptosis can also be induced by 2ME2. The activities ascribed to 2ME2 have implicated its use in diseases with inflammatory components, such as rheumatoid arthritis (RA). EntreMed and its collaborators have now established the dose-dependent, anti-arthritic activity of 2ME2 following oral administration in four distinct animal models of RA. This activity has been manifested as an inhibition in the infiltration of inflammatory cells, pannus formation, cartilage lesions, and bone resorption.

The initial formulation of 2ME2, Panzem® capsules, has been administered to more than 171 patients in six phase I and II oncology trials and has shown an excellent safety profile with no dose limiting toxicities reported to date. EntreMed has reformulated 2ME2 as an orally administered liquid suspension (Panzem® NCD) to increase plasma drug levels in patients. In preclinical toxicity studies, the liquid suspension formulation demonstrated no additional toxicity. Based on these results, EntreMed has initiated IND-enabling studies for 2ME2 in RA.

—A. Techman