Randomized Phase 2 Study of IMC-A12 for HER2-Expressing Advanced Breast Cancer Commences Patient Enrollment

Randomized Phase 2 Study of IMC-A12 for HER2-Expressing Advanced Breast Cancer Commences Patient Enrollment

NEW YORK--(BUSINESS WIRE)--ImClone Systems Incorporated (NASDAQ: IMCL), a global leader in the development and commercialization of novel antibodies to treat cancer, today announced that its disease-directed randomized Phase 2 clinical trial of IMC-A12 in patients with previously treated HER2-expressing locally advanced or metastatic breast cancer has commenced patient enrollment. IMC-A12 is ImClone's fully human, IgG1 anti-insulin-like growth factor-1 receptor (IGF-1R) monoclonal antibody.

The primary objective of this Phase 2 study is to evaluate the antitumor activity of the combination of capecitabine and lapatinib with and without IMC-A12 in patients with HER2-expressing Stages IIIB, IIIC, or IV breast cancer that has progressed on trastuzumab-containing treatment. This study is being conducted by the North Central Cancer Treatment Group (NCCTG), a national clinical research group sponsored by the National Cancer Institute (NCI). NCCTG is comprised of a network of more than 1,000 community-based cancer treatment clinics in the United States, Canada and Mexico that work with Mayo Clinic to conduct clinical studies for advancing cancer treatment. Other Cooperative Groups are assisting NCCTG to recruit patients, via the CTSU (NCI's CANcer Therapy Study Unit). This study is one of at least 10 Phase 1 and 2 clinical trials of IMC-A12 sponsored by the Cancer Therapy Evaluation Program (CTEP) of the Division of Cancer Treatment and Diagnosis (DCTD), NCI. ImClone announced the selection of these proposals by NCI in September 2007.

"This study of IMC-A12 is a rationally designed study based on preclinical evidence suggesting that there are interactions between the HER2 and IGF-IR that may be exploited to improve treatment outcome for women with HER2-expressing breast cancer," said Eric K. Rowinsky, M.D., Chief Medical Officer and Executive Vice President of ImClone. "The NCCTG is seeking to determine if the anticancer activity of the combination with lapatinib and capecitabine, which is an approved treatment for women with HER2-expressing breast cancer that is no longer responsive to trastuzumab, can be improved by the addition of IMC-A12."

This Phase 2 study of IMC-A12 will enroll approximately 154 patients at more than 140 sites across the U.S. Patients will be randomized to receive treatment with either capecitabine and lapatinib (one-third of the patients) or the same treatment plus IMC-A12 (two-thirds of the patients). Treatment in both arms will be continued as long as potential benefit is shown. The primary endpoint of the study is progression-free survival.

"Research asserts that HER2-positive breast tumors may resort to the IGF-1R pathway as an adaptive growth mechanism to therapies that target the HER2 cell proliferation mechanism," said Paul Haluska, M.D., Ph.D. Assistant Professor of Oncology at Mayo Clinic and the lead scientist on the Phase 2 study. "The IGF-R pathway is a key mechanism of resistance in cancers that adapt to HER2-targeted therapy, as well as chemotherapy. Now that we have a therapeutic agent in IMC-A12 to block IGF-1R, we are able to conduct this study to determine if co-inhibiting IGF-1R and HER2 in combination with the chemotherapy agent capecitabine will benefit patients with HER2-positive breast cancers."

NCCTG is dedicated to bringing clinical trials with promising new cancer therapies to communities where patients live. NCCTG specializes in researching methods of treating and preventing cancer, and in researching methods to alleviate the side effects of cancer and cancer treatments. For more information about NCCTG, please visit http://ncctg.mayo.edu [1].

IMC-A12 is a fully human IgG1 monoclonal antibody. It is designed to specifically target the human IGF-1R, thereby inhibiting certain ligands known as IGF-1 and -2 from binding to and activating the receptor. This action blocks a signaling pathway that enhances tumor cell proliferation and survival. In 2007, ImClone completed enrollment into two Phase 1 studies of IMC-A12, which demonstrated favorable safety and pharmacokinetic profiles, as well as preliminary evidence of antitumor activity as a single agent when administered either weekly or every two weeks. In addition to this Phase 2 study of IMC-A12, Phase 2 studies of IMC-A12 in patients with soft tissue sarcoma (adults and adolescents), hormone expressing advanced breast cancer, and advanced prostate (first-and second-line studies), pancreatic, colorectal, liver, head and neck cancers, as well as a series of Phase 1/2 studies in pediatric malignancies and others evaluating the combination of IMC-A12 and temsirolimus, have begun to enroll patients. Additional disease-directed studies of IMC-A12 sponsored by both ImClone and the NCI under a development agreement are advancing towards initiation.

About ImClone's NCI-Sponsored IMC-A12 Trials

In September 2007, the CTEP of the DCTD, NCI selected 10 proposals for Phase 1 and 2 clinical trials of ImClone's IMC-A12, and several other proposals have been selected since that time. The selection of the proposed trials followed NCI's solicitation for specific disease-directed studies among NCI investigators at academic institutions, clinical trial consortia and NCI-sponsored oncology cooperative clinical trial groups in the U.S. The selected trials represent the first stage of clinical evaluations of IMC-A12 sponsored by CTEP, NCI under a Clinical Trials Agreement between ImClone and DCTD, NCI to facilitate the clinical development of IMC-A12. Both randomized and nonrandomized Phase 2 trials sponsored by CTEP will explore the clinical activity, pharmacology and biological effects of IMC-A12 as a single agent or combined with other relevant anticancer agents in a wide range of malignancies including breast, lung, pancreas and liver cancers, as well as both adult and pediatric sarcomas. In addition, Phase 1/2 studies will evaluate the safety, pharmacology, anticancer activity and biological effects of IMC-A12 in children and adolescents with cancer, as well as in combination with other novel targeting agents in which there is a specific rationale for combined use.

About ImClone Systems

ImClone Systems Incorporated is a fully integrated global biopharmaceutical company committed to advancing oncology care by developing and commercializing a portfolio of targeted biologic treatments designed to address the medical needs of patients with a variety of cancers. The Company's research and development programs include growth factor blockers and angiogenesis inhibitors. ImClone Systems' headquarters and research operations are located in New York City, with additional administration and manufacturing facilities in Branchburg, New Jersey. For more information about ImClone Systems, please visit the Company's web site at http://www.imclone.com.

Certain matters discussed in this news release may constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and the Federal securities laws. Although the company believes that the expectations reflected in such forward-looking statements are based upon reasonable assumptions it can give no assurance that its expectations will be achieved. Forward-looking information is subject to certain risks, trends and uncertainties that could cause actual results to differ materially from those currently expected. Many of these factors are beyond the company's ability to control or predict. Important factors that may cause actual results to differ materially and could impact the company and the statements contained in this news release can be found in the company's filings with the Securities and Exchange Commission, particularly those factors identified as "risk factors" in the Company's most recent annual report of Form 10-K and in its quarterly reports on Form 10-Q and current reports on Form 8-K. For forward-looking statements in this news release, the company claims the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995. The company assumes no obligation to update or supplement any forward-looking statements whether as a result of new information, future events or otherwise.