Panzem® is an orally active, well-tolerated compound that has antiproliferative, antiangiogenic and anti-inflammatory properties. Panzem® attacks tumor cells through multiple mechanisms of action (MOA) and blocks the development of new blood vessels that feed tumor cells.
Panzem’s MOAs include the disruption of angiogenesis through the inhibition of hypoxia inducible factor-1 alpha (HIF-1α), a protein required for angiogenesis and cell survival under stress. The inhibition of angiogenesis is an important approach to the treatment of both cancer and rheumatoid arthritis. Initial development of 2ME2 has been focused on various oncology indications. While modest antitumor activity has been demonstrated across most clinical studies, there is no clear development path that would allow the Company to narrow the indications for the next series of larger randomized studies. Panzem® for oncology is a drug candidate that needs to be developed in combination with other chemotherapeutic agents, requiring the conduct of further non-randomized trials to clarify specific combinations and indications. Conversely, Panzem® has potential as a single agent in rheumatoid arthritis based on its antiangiogenic, antiiflammatory, and antiosteoclastic (bone resorption) properties.

Based on the knowledge gained from the oncology development effort and favorable preclinical research results showing that 2ME2 has disease modifying or “DMARD” activity, EntreMed plans to move 2ME2 forward in rheumatoid arthritis. DMARDs are drugs that have the ability to slow down disease progression in rheumatoid arthritis and other autoimmune diseases. EntreMed has generated substantial preclinical data demonstrating the positive effects of 2ME2 treatment on inflammation and disease progression in well-accepted RA models. Radiographic and immunohistochemical staining results from these preclinical trials have shown consistent inhibitory effects on the hallmarks of the disease, including the inhibition of the highly angiogenic pannus, infiltrating cells, cartilage lesions and bone resorption.

EntreMed believes that an opportunity exists for 2ME2, based on its antiangiogenic activity and safety profile, to become a novel, non-immunosuppressive DMARD for the treatment of RA. The Company continues to invest behind the development of Panzem® for rheumatoid arthritis, potentially adding another large market opportunity to its pipeline.

The FDA has accepted EntreMed’s IND for 2ME2 in RA, which included an extensive human safety dossier in 300 patients from the oncology studies. Panzem® for RA represents a safe, orally administered, small molecule alternative to current biologicals and a potential “first-in-class” cross-over opportunity from oncology. The Company plans to initiate a normal volunteer clinical trial in 2008 and seek a development partner to manage larger multi-arm Phase 2 and Phase 3 studies.