ImClone Presents Promising Phase I Data on Two Pipeline Antibodies For Cancer Therapy

ImClone Systems, Inc., (IMCL) announced promising phase I data on two of the company's fully-human, Immunoglobulin G 1 (IgG1) monoclonal antibodies, IMC-1121B and IMC-11F8, at the American Society of Clinical Oncology 42nd annual meeting. The first of these antibodies, IMC-1121B, aims to inhibit the function of a signaling pathway known to play a role in the formation of blood vessels in tumors - a process known as angiogenesis - by blocking the vascular endothelial growth factor receptor-2 (VEGFR-2) from binding to molecules (ligands) that stimulate its activation.

A phase I study was designed to characterize the principal toxicities, dose-limiting toxicity, and maximum tolerated dose of IMC-1121B, as well as assess any preliminary evidence of antitumor activity. To date, a total of 14 patients with advanced cancer have been enrolled in the study at varying dose levels. The most frequent adverse events were anorexia, vomiting, anemia, depression, fatigue, and insomnia. Preliminary results of the study suggest that the toxicity profile of IMC-1121B is distinct from other VEGF pathway inhibitors and that its pharmacokinetic profile is similar to other growth factor receptor pathway antibodies. Further, promising early evidence of antitumor activity was observed, where one patient experienced a partial response and five patients had stable disease. Dose escalation continues and imaging and biological endpoints are in process.

The second antibody, IMC-11F8, is a high-affinity antibody that blocks liganddependent activation of the epidermal growth factor receptor (EGFR). EGFR is part of a signaling pathway that is linked to the growth, development, and survival of many human cancer cells. Studies have shown that the inhibition of EGFR with an IgG1 antibody blocks phosphorylation, resulting in the inhibition of cell growth, the induction of cell death, a decreased ability to form tumor vasculature, and the recruitment of the body's immune defenses to attack cancer cells.

A phase I study is being conducted to determine the safety profile and recommended dose of IMC-11F8. To date, 31 out of 40 planned patients with advanced solid tumors who are refractory to, or have no available, standard therapy have been enrolled at various dose levels. The most frequent adverse events were nausea, vomiting, fatigue, and headache. No infusion reactions were observed. Although a maximum tolerated dose has not been established, IMC- 11F8 has shown activity at two different dose levels.

"These antibodies are among several targeted therapies in development at ImClone Systems that give us a uniquely valuable pipeline within the industry," stated Eric K. Rowinsky, MD, chief medical officer of ImClone Systems. "We are very excited about the antitumor activity demonstrated by both of these compounds at this early stage of testing. Because the proof of principle for both of these antibodies has been well established by commercially available therapies, we are optimistic that phase III testing can begin shortly after phase I is
complete."

The exclusive rights to market IMC-11F8 outside the United States and Canada and coexclusive development rights in Japan belong to ImClone Systems, while commercial rights to the antibody in the U.S., Canada, and Japan fall within the scope of ImClone Systems' commercial agreement with Bristol-Myers Squibb regarding ERBITUX. Commercial rights to IMC-1121B have not been partnered.