EntreMed, Inc., a clinical-stage pharmaceutical company developing therapeutics for the treatment of cancer and inflammatory diseases, has commenced a Phase 1 clinical trial to evaluate the safety, tolerability, pharmacokinetics, and clinical benefit of its novel tubulin binding agent, ENMD-1198, in patients with advanced cancer.

Patients with advanced cancer whose disease has failed to respond to existing therapies or where no approved therapy is available are expected to be enrolled in the study. The single-centre, dose-escalation study will be conducted at the University of Colorado at Denver and Health Sciences Centre in Aurora, Colorado.

ENMD-1198, a new chemical entity (NCE) based on a modified chemical structure of 2-methoxyestradiol (2ME2), is designed to decrease metabolism while retaining 2ME2's multiple mechanisms of action, including inducing apoptosis, binding microtubules, and inhibiting HIF-1á. In preclinical studies, ENMD-1198 has been shown to be an orally active, microtubule disrupting agent that leads to arrest of cell division and apoptosis in tumour cells. In addition, ENMD-1198 also exerts antiangiogenic activity that further contributes to its overall anti-tumour effects. Preclinical results for
ENMD-1198 support its potential for broad application in cancer. ENMD-1198 was discovered at EntreMed and the intellectual property belongs exclusively to the company, stated a release.

Carolyn F. Sidor, EntreMed's VP and Chief Medical Officer said, "Results from preclinical studies with this compound highlight its significant anti-tumour activity and multiple mechanisms of action, including inhibiting three transcription factors, HIF-1á, NF-êB and Stat3, known to promote tumorigenesis. With the initiation of this study, EntreMed now has three product candidates, Panzem NCD, MKC-1 and ENMD-1198, in clinical trials for cancer patients, with additional trials planned for later this year."

According to the release, preclinical data demonstrate that oral administration of ENMD-1198 leads to pronounced in vivo anti-tumour activity in several cancer models, resulting in a reduction in tumour burden and/or an increase in survival equivalent to cyclophosphamide, the positive control in the studies. Preclinical toxicology studies demonstrate that ENMD-1198 affects cell populations with a high proliferative rate, including bone marrow, gastrointestinal tract and lymphoid organs. These effects are common with approved cancer agents and can be monitored in the clinic.